Enhancing Solubility and Bioefficacy of Stilbenes by Liposomal Encapsulation─The Case of Macasiamenene F

Click to copy article linkArticle link copied!

This article references 68 other publications.

1. 1

   Alskär, L. C.; Porter, C. J. H.; Bergström, C. A. S. Tools for Early Prediction of Drug Loading in Lipid-Based Formulations. Mol. Pharmaceutics 2016, 13 (1), 251– 261,  DOI: 10.1021/acs.molpharmaceut.5b00704

   Google Scholar

   1

   Tools for Early Prediction of Drug Loading in Lipid-Based Formulations

   Alskar Linda C; Bergstrom Christel A S; Porter Christopher J H; Bergstrom Christel A S

   Molecular pharmaceutics (2016), 13 (1), 251-61 ISSN:.

   Identification of the usefulness of lipid-based formulations (LBFs) for delivery of poorly water-soluble drugs is at date mainly experimentally based. In this work we used a diverse drug data set, and more than 2,000 solubility measurements to develop experimental and computational tools to predict the loading capacity of LBFs. Computational models were developed to enable in silico prediction of solubility, and hence drug loading capacity, in the LBFs. Drug solubility in mixed mono-, di-, triglycerides (Maisine 35-1 and Capmul MCM EP) correlated (R(2) 0.89) as well as the drug solubility in Carbitol and other ethoxylated excipients (PEG400, R(2) 0.85; Polysorbate 80, R(2) 0.90; Cremophor EL, R(2) 0.93). A melting point below 150 °C was observed to result in a reasonable solubility in the glycerides. The loading capacity in LBFs was accurately calculated from solubility data in single excipients (R(2) 0.91). In silico models, without the demand of experimentally determined solubility, also gave good predictions of the loading capacity in these complex formulations (R(2) 0.79). The framework established here gives a better understanding of drug solubility in single excipients and of LBF loading capacity. The large data set studied revealed that experimental screening efforts can be rationalized by solubility measurements in key excipients or from solid state information. For the first time it was shown that loading capacity in complex formulations can be accurately predicted using molecular information extracted from calculated descriptors and thermal properties of the crystalline drug.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28vhvF2qtg%253D%253D&md5=8740b7ba28190e9752971ee249383f39
2. 2

   Savjani, K. T.; Gajjar, A. K.; Savjani, J. K. Drug Solubility: Importance and Enhancement Techniques. ISRN Pharm. 2012, 2012, 195727  DOI: 10.5402/2012/195727

   Google Scholar

   2

   Drug solubility: importance and enhancement techniques

   Savjani Ketan T; Gajjar Anuradha K; Savjani Jignasa K

   ISRN pharmaceutics (2012), 2012 (), 195727 ISSN:.

   Solubility, the phenomenon of dissolution of solute in solvent to give a homogenous system, is one of the important parameters to achieve desired concentration of drug in systemic circulation for desired (anticipated) pharmacological response. Low aqueous solubility is the major problem encountered with formulation development of new chemical entities as well as for the generic development. More than 40% NCEs (new chemical entities) developed in pharmaceutical industry are practically insoluble in water. Solubility is a major challenge for formulation scientist. Any drug to be absorbed must be present in the form of solution at the site of absorption. Various techniques are used for the enhancement of the solubility of poorly soluble drugs which include physical and chemical modifications of drug and other methods like particle size reduction, crystal engineering, salt formation, solid dispersion, use of surfactant, complexation, and so forth. Selection of solubility improving method depends on drug property, site of absorption, and required dosage form characteristics.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38fpslGjsg%253D%253D&md5=5dce666f4aaa82df009fcc5edeb9ff79
3. 3

   Bonechi, C.; Martini, S.; Ciani, L.; Lamponi, S.; Rebmann, H.; Rossi, C.; Ristori, S. Using Liposomes as Carriers for Polyphenolic Compounds: The Case of Trans-Resveratrol. PLoS One 2012, 7 (8), e41438  DOI: 10.1371/journal.pone.0041438

   Google Scholar

   3

   Using liposomes as carriers for polyphenolic compounds: the case of trans-resveratrol

   Bonechi, Claudia; Martini, Silvia; Ciani, Laura; Lamponi, Stefania; Rebmann, Herbert; Rossi, Claudio; Ristori, Sandra

   PLoS One (2012), 7 (8), e41438CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)

   Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol found in various plants, esp. in the skin of red grapes. The effect of resveratrol on human health is the topic of numerous studies. In fact this mol. has shown anti-cancer, anti-inflammatory, blood-sugar-lowering ability and beneficial cardiovascular effects. However, for many polyphenol compds. of natural origin bioavailability is limited by low soly. in biol. fluids, as well as by rapid metabolization in vivo. Therefore, appropriate carriers are required to obtain efficient therapeutics along with low administration doses. Liposomes are excellent candidates for drug delivery purposes, due to their biocompatibility, wide choice of physico-chem. properties and easy prepn. In this paper liposome formulations made by a satd. phosphatidyl-choline (DPPC) and cholesterol (or its pos. charged deriv. DC-CHOL) were chosen to optimize the loading of a rigid hydrophobic mol. such as resveratrol. Plain and resveratrol loaded liposomes were characterized for size, surface charge and structural details by complementary techniques, i.e. Dynamic Light Scattering (DLS), Zeta potential and Small Angle X-ray Scattering (SAXS). Nuclear and Electron Spin magnetic resonances (NMR and ESR, resp.) were also used to gain information at the mol. scale. The obtained results allowed to give an account of loaded liposomes in which resveratrol interacted with the bilayer, being more deeply inserted in cationic liposomes than in zwitterionic liposomes. Relevant properties such as the mean size and the presence of oligolamellar structures were influenced by the loading of RESV guest mols. The toxicity of all these systems was tested on stabilized cell lines (mouse fibroblast NIH-3T3 and human astrocytes U373-MG), showing that cell viability was not affected by the administration of liposomal resveratrol.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1GqsbrF&md5=27ba907aae177ec306039916d0be812f
4. 4

   Lee, M.-K. Liposomes for Enhanced Bioavailability of Water-Insoluble Drugs: In Vivo Evidence and Recent Approaches. Pharmaceutics 2020, 12 (3), 264,  DOI: 10.3390/pharmaceutics12030264

   Google Scholar

   4

   Liposomes for enhanced bioavailability of water-insoluble drugs: in vivo evidence and recent approaches

   Lee, Mi-Kyung

   Pharmaceutics (2020), 12 (3), 264CODEN: PHARK5; ISSN:1999-4923. (MDPI AG)

   It has been known that a considerable no. of drugs in clin. use or under development are water-insol. drugs with poor bioavailability (BA). The liposomal delivery system has drawn attention as one of the noteworthy approaches to increase dissoln. and subsequently absorption in the gastrointestinal (GI) tract because of its biocompatibility and ability to encapsulate hydrophobic mols. in the lipid domain. However, there have been several drawbacks, such as structural instability in the GI tract and poor permeability across intestinal epithelia because of its relatively large size. In addn., there have been no liposomal formulations approved for oral use to date, despite the success of parenteral liposomes. Nevertheless, liposomal oral delivery has resurged with the rapid increase of published studies in the last decade. However, it is discouraging that most of this research has been in vitro studies only and there have not been many water-insol. drugs with in vivo data. The present review focused on the in vivo evidence for the improved BA of water-insol. drugs using liposomes to resolve doubts raised concerning liposomal oral delivery and attempted to provide insight by highlighting the approaches used for in vivo achievements.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtleqtrzE&md5=06b12d5f07d722ce1d8b8a43c8074857
5. 5

   Balouch, M.; Storchmannová, K.; Štěpánek, F.; Berka, K. Computational Prodrug Design Methodology for Liposome Formulability Enhancement of Small-Molecule APIs. Mol. Pharmaceutics 2023, 20, 2119,  DOI: 10.1021/acs.molpharmaceut.2c01078

   Google Scholar

   5

   Computational Prodrug Design Methodology for Liposome Formulability Enhancement of Small-Molecule APIs

   Balouch, Martin; Storchmannova, Katerina; Stepanek, Frantisek; Berka, Karel

   Molecular Pharmaceutics (2023), 20 (4), 2119-2127CODEN: MPOHBP; ISSN:1543-8384. (American Chemical Society)

   Encapsulation into liposomes is a formulation strategy that can improve efficacy and reduce side effects of active pharmaceutical ingredients (APIs) that exhibit poor biodistribution or pharmacokinetics when administered alone. However, many APIs are unsuitable for liposomal formulations intended for parenteral administration due to their inherent physicochem. properties-lipid bilayer permeability and water-lipid equil. partitioning coeff. Too high permeability results in premature leakage from liposomes, while too low permeability means the API is not able to pass across biol. barriers. There are several options for solving this issue: (i) change of the lipid bilayer compn., (ii) addn. of a permeability enhancer, or (iii) modification of the chem. structure of the API to design a prodrug. The latter approach was taken in the present work, and the effect of small changes in the mol. structure of the API on its permeation rate across a lipidic bilayer was systematically explored utilizing computer simulations. An in silico methodol. for prodrug design based on the COSMOperm approach has been proposed and applied to four APIs (abiraterone, cytarabine, 5-fluorouracil, and paliperidone). It is shown that the addn. of aliph. hydrocarbon chains via ester or amide bonds can render the mol. more lipophilic and increase its permeability by approx. 1 order of magnitude for each 2 carbon atoms added, while the formation of fructose adducts can provide a more hydrophilic character to the mol. and reduce its lipid partitioning. While partitioning was found to depend only on the size and type of the added group, permeability was found to depend also on the added group location. Overall, it has been shown that both permeability and lipid partitioning coeff. can be systematically shifted into the desired liposome formulability window by appropriate group contributions to the parental drug. This can significantly increase the portfolio of APIs for which liposome or lipid nanoparticle formulations become feasible.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXlsVajt7s%253D&md5=67152c6e297c5566f97d5276ce5511da
6. 6

   Zylberberg, C.; Matosevic, S. Pharmaceutical Liposomal Drug Delivery: A Review of New Delivery Systems and a Look at the Regulatory Landscape. Drug Delivery 2016, 23 (9), 3319– 3329,  DOI: 10.1080/10717544.2016.1177136

   Google Scholar

   6

   Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape

   Zylberberg, Claudia; Matosevic, Sandro

   Drug Delivery (2016), 23 (9), 3319-3329CODEN: DDELEB; ISSN:1071-7544. (Taylor & Francis Ltd.)

   Liposomes were the first nanoscale drug to be approved for clin. use in 1995. Since then, the technol. has grown considerably, and pioneering recent work in liposome-based delivery systems has brought about remarkable developments with significant clin. implications. This includes long-circulating liposomes, stimuli-responsive liposomes, nebulized liposomes, elastic liposomes for topical, oral and transdermal delivery and covalent lipid-drug complexes for improved drug plasma membrane crossing and targeting to specific organelles. While the regulatory bodies' opinion on liposomes is well-documented, current guidance that address new delivery systems are not. This review describes, in depth, the current state-of-the-art of these new liposomal delivery systems and provides a crit. overview of the current regulatory landscape surrounding commercialization efforts of higher-level complexity systems, the expected requirements and the hurdles faced by companies seeking to bring novel liposome-based systems for clin. use to market.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XntlKntrw%253D&md5=3c46bc993c2ddcedca6938049a40dcf3
7. 7

   Khan, A. R.; Yang, X.; Fu, M.; Zhai, G. Recent Progress of Drug Nanoformulations Targeting to Brain. J. Controlled Release 2018, 291, 37– 64,  DOI: 10.1016/j.jconrel.2018.10.004

   Google Scholar

   7

   Recent progress of drug nanoformulations targeting to brain

   Khan, Abdur Rauf; Yang, Xiaoye; Fu, Manfei; Zhai, Guangxi

   Journal of Controlled Release (2018), 291 (), 37-64CODEN: JCREEC; ISSN:0168-3659. (Elsevier B.V.)

   Most of the potential therapeutic agents capable to modulate the pathophysiol. or treat the neurol. disorders and brain tumors are useless in the current modern and advanced era of neuroscience due to the impeding action of biol. barriers. Among various therapeutic strategies applied for translocation of drug delivery across the blood-brain barrier (BBB), nanoformulations set an excellent platform for brain targeting by overcoming the biol. and chem. barriers and protecting drug from efflux to promote the optimum therapeutic drug concn. in brain parenchyma tissues. Nanocarriers are the most widely studied delivery vehicles for BBB translocation with the efficiency of selectively targeting or exploiting inherent biol. mols., receptors, carriers or mechanisms of the brain. Nearly all of the available drug delivery nanocarriers explored in recent years for brain therapeutics and theranostics are based on lipid or polymeric materials. Polymeric nanoparticles (NPs) and lipid based nanocarriers including liposomes, solid lipid NPs (SLNs) and micelles, etc. are under the direct focus of neuroscientists due to the promising attributes and vast applications in neurol. disorders. Surface modification of nanovehicles with proper targeting moiety or coating with surfactants promotes the interaction with endothelial cells and passage of nanocarriers to the brain. This review comprehensively depicts challenges to the brain targeted drug delivery, mechanisms of drug transportation across the BBB, and potential contributions of endogenous cells as NPs delivery cells and novel targeting ligands decorated nanoformulations in imaging, treating and controlling neurol. disorders.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhvFKit7nN&md5=08579639bf7fbec2a428ba5b9a458e1f
8. 8

   Bruch, G. E.; Fernandes, L. F.; Bassi, B. L. T.; Alves, M. T. R.; Pereira, I. O.; Frézard, F.; Massensini, A. R. Liposomes for Drug Delivery in Stroke. Brain Res. Bull. 2019, 152, 246– 256,  DOI: 10.1016/j.brainresbull.2019.07.015

   Google Scholar

   8

   Liposomes for drug delivery in stroke

   Bruch, Gisele E.; Fernandes, Lorena F.; Bassi, Beatriz L. T.; Alves, Marco Tullio R.; Pereira, Isabelle O.; Frezard, Frederic; Massensini, Andre R.

   Brain Research Bulletin (2019), 152 (), 246-256CODEN: BRBUDU; ISSN:0361-9230. (Elsevier)

   A review. Stroke is one of the leading causes of mortality and morbidity worldwide. Due to its poor prognosis, there is a major neg. impact on the patients and their familys life quality. However, despite the severity of this pathol. tissue plasminogen activator (tPA) is the only FDA approved treatment for ischemic stroke. Moreover, there is no effective treatment for hemorrhagic stroke and only some palliative procedures are often performed to improve the patients quality of life. Considering this, nanotechnol. can offer some advantages for the development of new therapies for stroke. Among the various types of nanomaterials, liposomes are the most extensively studied due to their biocompatibility, biodegradability, and low toxicity. Liposomes, as a drug delivery system, are able to mask therapeutic compds. and allow their passage through the blood-brain barrier. Liposomes also protect drugs from degrdn. in a biol. environment, increasing the circulation time and accumulation in the target tissue. Hence, this review highlights the potential of liposomes applications for delivery of therapeutic compds. for treating stroke.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsFWrtbzF&md5=6b266988ab8d442ad19a03aa255a9b4d
9. 9

   Monteiro, N.; Martins, A.; Reis, R. L.; Neves, N. M. Liposomes in Tissue Engineering and Regenerative Medicine. J. R. Soc. Interface 2014, 11 (101), 20140459  DOI: 10.1098/rsif.2014.0459

   Google Scholar

   9

   Liposomes in tissue engineering and regenerative medicine

   Monteiro Nelson; Martins Albino; Reis Rui L; Neves Nuno M

   Journal of the Royal Society, Interface (2014), 11 (101), 20140459 ISSN:.

   Liposomes are vesicular structures made of lipids that are formed in aqueous solutions. Structurally, they resemble the lipid membrane of living cells. Therefore, they have been widely investigated, since the 1960s, as models to study the cell membrane, and as carriers for protection and/or delivery of bioactive agents. They have been used in different areas of research including vaccines, imaging, applications in cosmetics and tissue engineering. Tissue engineering is defined as a strategy for promoting the regeneration of tissues for the human body. This strategy may involve the coordinated application of defined cell types with structured biomaterial scaffolds to produce living structures. To create a new tissue, based on this strategy, a controlled stimulation of cultured cells is needed, through a systematic combination of bioactive agents and mechanical signals. In this review, we highlight the potential role of liposomes as a platform for the sustained and local delivery of bioactive agents for tissue engineering and regenerative medicine approaches.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2M3oslKitw%253D%253D&md5=f9b0273050f5d4a99abfde104cd21f16
10. 10

    Inglut, C. T.; Sorrin, A. J.; Kuruppu, T.; Vig, S.; Cicalo, J.; Ahmad, H.; Huang, H.-C. Immunological and Toxicological Considerations for the Design of Liposomes. Nanomaterials 2020, 10 (2), 190,  DOI: 10.3390/nano10020190

    Google Scholar

    10

    Immunological and toxicological considerations for the design of liposomes

    Inglut, Collin T.; Sorrin, Aaron J.; Kuruppu, Thilinie; Vig, Shruti; Cicalo, Julia; Ahmad, Haroon; Huang, Huang-Chiao

    Nanomaterials (2020), 10 (2), 190CODEN: NANOKO; ISSN:2079-4991. (MDPI AG)

    A review. Liposomes hold great potential as gene and drug delivery vehicles due to their biocompatibility and modular properties, coupled with the major advantage of attenuating the risk of systemic toxicity from the encapsulated therapeutic agent. Decades of research have been dedicated to studying and optimizing liposomal formulations for a variety of medical applications, ranging from cancer therapeutics to analgesics. Some effort has also been made to elucidate the toxicities and immune responses that these drug formulations may elicit. Notably, i.v. injected liposomes can interact with plasma proteins, leading to opsonization, thereby altering the healthy cells they come into contact with during circulation and removal. Addnl., due to the pharmacokinetics of liposomes in circulation, drugs can end up sequestered in organs of the mononuclear phagocyte system, affecting liver and spleen function. Importantly, liposomal agents can also stimulate or suppress the immune system depending on their physiochem. properties, such as size, lipid compn., pegylation, and surface charge. Despite the surge in the clin. use of liposomal agents since 1995, there are still several drawbacks that limit their range of applications. This review presents a focused anal. of these limitations, with an emphasis on toxicity to healthy tissues and unfavorable immune responses, to shed light on key considerations that should be factored into the design and clin. use of liposomal formulations.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlsVymtbw%253D&md5=2b30c979dbdbcc12ed5ddbc0fa27e9fb
11. 11

    Daraee, H.; Etemadi, A.; Kouhi, M.; Alimirzalu, S.; Akbarzadeh, A. Application of Liposomes in Medicine and Drug Delivery. Artif. Cells Nanomed. Biotechnol. 2016, 44 (1), 381– 391,  DOI: 10.3109/21691401.2014.953633

    Google Scholar

    11

    Application of liposomes in medicine and drug delivery

    Daraee, Hadis; Etemadi, Ali; Kouhi, Mohammad; Alimirzalu, Samira; Akbarzadeh, Abolfazl

    Artificial Cells, Nanomedicine, and Biotechnology (2016), 44 (1), 381-391CODEN: ACNBCI; ISSN:2169-141X. (Taylor & Francis Ltd.)

    A review. Liposomes provide an established basis for the sustainable development of different com. products for treatment of medical diseases by the smart delivery of drugs. The industrial applications include the use of liposomes as drug delivery vehicles in medicine, adjuvants in vaccination, signal enhancers/carriers in medical diagnostics and anal. biochem., solubilizers for various ingredients as well as support matrixes for various ingredients and penetration enhancers in cosmetics. In this review, we summarize the main applications and liposome-based com. products that are currently used in the medical field.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xht12qs7k%253D&md5=3d529ef60cfba8499185b5dd6625ae8d
12. 12

    Sercombe, L.; Veerati, T.; Moheimani, F.; Wu, S. Y.; Sood, A. K.; Hua, S. Advances and Challenges of Liposome Assisted Drug Delivery. Front. Pharmacol. 2015, 6, 286  DOI: 10.3389/fphar.2015.00286

    Google Scholar

    12

    Advances and challenges of liposome assisted drug delivery

    Sercombe, Lisa; Veerati, Tejaswi; Moheimani, Fatemeh; Wu, Sherry Y.; Sood, Anil K.; Hua, Susan

    Frontiers in Pharmacology (2015), 6 (), 286/1-286/13CODEN: FPRHAU; ISSN:1663-9812. (Frontiers Media S.A.)

    The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compds., overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compds. to target sites in vivo. This enables effective delivery of encapsulated compds. to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochem. and biophys. properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of pos. results in preclin. studies, the clin. translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biol. challenges that still remain, and current clin. and exptl. use of liposomes for biomedical applications. The translational obstacles of liposomal technol. will also be presented.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlaqsrnE&md5=4a475019a1cae3a07587d47f2fae92a0
13. 13

    Bulbake, U.; Doppalapudi, S.; Kommineni, N.; Khan, W. Liposomal Formulations in Clinical Use: An Updated Review. Pharmaceutics 2017, 9 (2), 12,  DOI: 10.3390/pharmaceutics9020012

    Google Scholar

    13

    Liposomal formulations in clinical use: an updated review

    Bulbake, Upendra; Doppalapudi, Sindhu; Kommineni, Nagavendra; Khan, Wahid

    Pharmaceutics (2017), 9 (2), 12/1-12/33CODEN: PHARK5; ISSN:1999-4923. (MDPI AG)

    Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clin. applications. These closed bilayer phospholipid vesicles have witnessed many tech. advances in recent years since their first development in 1965. Delivery of therapeutics by liposomes alters their biodistribution profile, which further enhances the therapeutic index of various drugs. Extensive research is being carried out using these nano drug delivery systems in diverse areas including the delivery of anti-cancer, anti-fungal, anti-inflammatory drugs and therapeutic genes. The significant contribution of liposomes as drug delivery systems in the healthcare sector is known by many clin. products, e.g., Doxil, Ambisome, DepoDur, etc. This review provides a detailed update on liposomal technologies e.g., DepoFoam Technol., Stealth technol., etc., the formulation aspects of clin. used products and ongoing clin. trials on liposomes.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsFOms7fP&md5=c7217956d0fbfbea417a0b393955db5a
14. 14

    Hornedo-Ortega, R.; Jourdes, M.; Da Costa, G.; Courtois, A.; Gabaston, J.; Teissedre, P.-L.; Richard, T.; Krisa, S. Oxyresveratrol and Gnetol Glucuronide Metabolites: Chemical Production, Structural Identification, Metabolism by Human and Rat Liver Fractions, and In Vitro Anti-Inflammatory Properties. J. Agric. Food Chem. 2022, 70 (41), 13082– 13092,  DOI: 10.1021/acs.jafc.1c07831

    Google Scholar

    14

    Oxyresveratrol and Gnetol Glucuronide Metabolites: Chemical Production, Structural Identification, Metabolism by Human and Rat Liver Fractions, and In Vitro Anti-inflammatory Properties

    Hornedo-Ortega, Ruth; Jourdes, Michael; Da Costa, Gregory; Courtois, Arnaud; Gabaston, Julien; Teissedre, Pierre-Louis; Richard, Tristan; Krisa, Stephanie

    Journal of Agricultural and Food Chemistry (2022), 70 (41), 13082-13092CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)

    Stilbene metabolites are attracting great interest because many of them exhibit similar or even stronger biol. effects than their parent compds. Furthermore, the metabolized forms are predominant in biol. fluids; therefore, their study is highly relevant. After hemisynthesis prodn., isolation, and structural elucidation, three glucuronide metabolites for oxyresveratrol (ORV) were formed: trans-ORV-4'-O-glucuronide, trans-ORV-3-O-glucuronide, and trans-ORV-2'-O-glucuronide. In addn., two glucuronide metabolites were obtained for gnetol (GN): trans-GN-2'-O-glucuronide and trans-GN-3-O-glucuronide. When the metab. of ORV and GN is studied in vitro by human and rat hepatic enzymes, four of the five hemisynthesized compds. were identified and quantified. Human enzymes glucuronidated preferably at the C-2' position, whereas rat enzymes do so at the C-3 position. In view of these kinetic findings, rat enzymes have a stronger metabolic capacity than human enzymes. Finally, ORV, GN, and their glucuronide metabolites (mainly at the C-3 position) decreased nitric oxide, reactive oxygen species, interleukin 1β, and tumor necrosis factor α prodn. in lipopolysaccharide-stimulated macrophages.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XksFKht7g%253D&md5=4df5c4cd5a0a2c44d0af7189044da048
15. 15

    Leláková, V.; Šmejkal, K.; Jakubczyk, K.; Veselý, O.; Landa, P.; Václavík, J.; Bobáľ, P.; Pížová, H.; Temml, V.; Steinacher, T.; Schuster, D.; Granica, S.; Hanáková, Z.; Hošek, J. Parallel in Vitro and in Silico Investigations into Anti-Inflammatory Effects of Non-Prenylated Stilbenoids. Food Chem. 2019, 285, 431– 440,  DOI: 10.1016/j.foodchem.2019.01.128

    Google Scholar

    15

    Parallel in vitro and in silico investigations into anti-inflammatory effects of non-prenylated stilbenoids

    Lelakova, Veronika; Smejkal, Karel; Jakubczyk, Karolina; Vesely, Ondrej; Landa, Premysl; Vaclavik, Jiri; Bobal, Pavel; Pizova, Hana; Temml, Veronika; Steinacher, Theresa; Schuster, Daniela; Granica, Sebastian; Hanakova, Zuzana; Hosek, Jan

    Food Chemistry (2019), 285 (), 431-440CODEN: FOCHDJ; ISSN:0308-8146. (Elsevier Ltd.)

    Stilbenoids represent a large group of bioactive compds., which occur in food and medicinal plants. Twenty-five stilbenoids were screened in vitro for their ability to inhibit COX-1, COX-2 and 5-LOX. Piceatannol and pinostilbene showed activity comparable to the zileuton and ibuprofen, resp. The anti-inflammatory potential of stilbenoids was further evaluated using THP-1 human monocytic leukemia cell line. Tests of the cytotoxicity on the THP-1 and HCT116 cell lines showed very low toxic effects. The tested stilbenoids were evaluated for their ability to attenuate the LPS-stimulated activation of NF-κB/AP-1. Most of the tested substances reduced the activity of NF-κB/AP-1 and later attenuated the expression of TNF-α. The effects of selected stilbenoids were further investigated on inflammatory signaling pathways. Non-prenylated stilbenoids regulated attenuation of NF-kB/AP-1 activity upstream by inhibiting the phosphorylation of MAPKs. A docking study used to in silico analyze the tested compds. confirmed their interaction with NF-kB, COX-2 and 5-LOX.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXjtVSqt7w%253D&md5=78f3351e612f7265b30a90fcf371a82a
16. 16

    Dvorakova, M.; Landa, P. Anti-Inflammatory Activity of Natural Stilbenoids: A Review. Pharmacol. Res. 2017, 124, 126– 145,  DOI: 10.1016/j.phrs.2017.08.002

    Google Scholar

    16

    Anti-inflammatory activity of natural stilbenoids: A review

    Dvorakova, Marcela; Landa, Premysl

    Pharmacological Research (2017), 124 (), 126-145CODEN: PHMREP; ISSN:1043-6618. (Elsevier Ltd.)

    A review. Resveratrol and other natural stilbenoids, including piceatannol, pterostilbene, and gnetol, are well-known anti-inflammatory compds. with indisputable activity in vitro as well as in vivo. Their mol. targets include inducible nitric oxide synthase, cyclooxygenases, leukotrienes, nuclear factor kappa B, tumor necrosis factor α, interleukins and many more. This anti-inflammatory activity together with their antioxidant activity is believed to stand behind their other pos. health effects against cancer, cardiovascular and neurodegenerative diseases or diabetes. Thus, they are nowadays com. marketed as nutraceuticals. Naturally, they are present in wine, grapes or berries. However, there is a rigorous debate about the real effect of these compds. on human health. It is argued that the concn. of stilbenoids in food and beverages is too low to have any therapeutic potential and this concn. is further reduced by their low bioavailability and extensive metab. Therefore, this review focuses on in vitro, in vivo, preclin. as well as clin. data available for various natural stilbenoids and summarizes the anti-inflammatory targets on mol. level, compares the relevance of the exptl. studies, discusses the metab. of stilbenoids and the potential activity of their metabolites and relates this knowledge to human health. Moreover, the ways to augment stilbenoids efficacy are suggested with special focus on multitargeted therapy and nanocarriers.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtlOgsbjI&md5=a86c67485938a20ae278c91e6d5fb58a
17. 17

    Bradamante, S.; Barenghi, L.; Villa, A. Cardiovascular Protective Effects of Resveratrol. Cardiovasc. Drug Rev. 2004, 22 (3), 169– 188,  DOI: 10.1111/j.1527-3466.2004.tb00139.x

    Google Scholar

    17

    Cardiovascular protective effects of resveratrol

    Bradamante, Silvia; Barenghi, Livia; Villa, Alessandro

    Cardiovascular Drug Reviews (2004), 22 (3), 169-188CODEN: CDREEA; ISSN:0897-5957. (Neva Press)

    A review. Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biol. and pharmacol. properties. It has been speculated that at low doses (such as consumed in the common diet) resveratrol may have cardioprotective activity. In this article we describe recent in vitro and in vivo studies in animal models. The results of these studies suggest that resveratrol modulates vascular cell function, inhibits LDL oxidn., suppresses platelet aggregation and reduces myocardial damage during ischemia-reperfusion. Although the reported biol. data indicate that resveratrol is a highly promising cardiovascular protective agent, more studies are needed to establish its bioavailability and in vivo cardioprotective effects, particularly in humans.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhtVSks7bF&md5=605583e067e53000e8647665888bb7d3
18. 18

    Chen, P.-C.; Tsai, W.-J.; Ueng, Y.-F.; Tzeng, T.-T.; Chen, H.-L.; Zhu, P.-R.; Huang, C.-H.; Shiao, Y.-J.; Li, W.-T. Neuroprotective and Antineuroinflammatory Effects of Hydroxyl-Functionalized Stilbenes and 2-Arylbenzo[b]Furans. J. Med. Chem. 2017, 60 (9), 4062– 4073,  DOI: 10.1021/acs.jmedchem.7b00376

    Google Scholar

    18

    Neuroprotective and Antineuroinflammatory Effects of Hydroxyl-Functionalized Stilbenes and 2-Arylbenzo[b]furans

    Chen, Pei-Chun; Tsai, Wei-Jern; Ueng, Yune-Fang; Tzeng, Tsai-Teng; Chen, Hsiang-Ling; Zhu, Pei-Ru; Huang, Chia-Hsiang; Shiao, Young-Ji; Li, Wen-Tai

    Journal of Medicinal Chemistry (2017), 60 (9), 4062-4073CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society)

    The drugs currently used to treat Alzheimer's disease (AD) are limited in the benefits they confer, and no medication has been clearly proven to cure or delay the progression of AD. Most candidate AD drugs are meant to reduce the prodn., aggregation, and toxicity of amyloid β (Aβ) or to promote Aβ clearance. Herein, we demonstrate the efficient synthesis of hydroxyl-functionalized stilbene and 2-arylbenzo[b]furan derivs. and report on the neuroprotective and anti-inflammatory effects of these phenolic compds. in vitro and in an animal model. Structure-activity relationships revealed that the presence of an acrylate group on 2-arylbenzo[b]furan confers neuroprotective and anti-inflammatory effects. Furthermore, compds. 11 and 37 in this study showed particular potential for development as disease-modifying anti-Alzheimer's drugs, based on their neuroprotective effects on neuron cells, their antineuroinflammatory effects on glial cells, and the ability to ameliorate nesting behavior in APP/PS1 mice. These results indicate that 2-arylbenzo[b]furans could be candidate compds. for the treatment of AD.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmvVSgu70%253D&md5=b96463cf6e4b20d9c607e372e7812c77
19. 19

    Biais, B.; Krisa, S.; Cluzet, S.; Da Costa, G.; Waffo-Teguo, P.; Mérillon, J.-M.; Richard, T. Antioxidant and Cytoprotective Activities of Grapevine Stilbenes. J. Agric. Food Chem. 2017, 65 (24), 4952– 4960,  DOI: 10.1021/acs.jafc.7b01254

    Google Scholar

    19

    Antioxidant and Cytoprotective Activities of Grapevine Stilbenes

    Biais, Benoit; Krisa, Stephanie; Cluzet, Stephanie; Da Costa, Gregory; Waffo-Teguo, Pierre; Merillon, Jean-Michel; Richard, Tristan

    Journal of Agricultural and Food Chemistry (2017), 65 (24), 4952-4960CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)

    Grapevine stem exts. are viticulture byproducts rich in stilbenes that are increasingly studied for their potential biol. activities. This study aimed to investigate some biol. activities of a grape byproduct with high stilbenoid content and to point out the mols. responsible of these beneficial activities. As a consequence, the ext. was subjected to a bioguided fractionation and sepn. by centrifugal partition chromatog. The obtained fractions were characterized by liq. chromatog. coupled to mass spectrometry and NMR. Fractions were purified further by column chromatog. and resulted in the purifn. of the main constituents. Thirteen stilbenes have been quantified. The most abundant compds. were ε-viniferin, resveratrol, and, in lesser amts., isohopeaphenol and ampelopsin A. The ext., fractions, and major stilbenes were tested for their antioxidant activity by oxygen radical absorbance capacity and their cyprotective effects against β-amyloid on rat pheochromocytoma cells. Among them, fraction 5 showed significant antioxidant activity and fraction 2 had a significant cytoprotective effect against β-amyloid-induced toxicity. Two putative inhibitors of β-amyloid toxicity have been identified: ampelopsin A and piceatannol.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXosVyjur0%253D&md5=5a6c771d3790e7101c9597f886b7ee9b
20. 20

    Vesely, O.; Baldovska, S.; Kolesarova, A. Enhancing Bioavailability of Nutraceutically Used Resveratrol and Other Stilbenoids. Nutrients 2021, 13 (9), 3095,  DOI: 10.3390/nu13093095

    Google Scholar

    20

    Enhancing Bioavailability of Nutraceutically Used Resveratrol and Other Stilbenoids

    Vesely, Ondrej; Baldovska, Simona; Kolesarova, Adriana

    Nutrients (2021), 13 (9), 3095CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)

    A review. Stilbenoids are interesting natural compds. with pleiotropic in vitro and in vivo activity. Their well-documented biol. properties include anti-inflammatory effects, anticancer effects, effects on longevity, and many others. Therefore, they are nowadays commonly found in foods and dietary supplements, and used as a part of treatment strategy in various types of diseases. Bioactivity of stilbenoids strongly depends on different types of factors such as dosage, food compn., and synergistic effects with other plant secondary metabolites such as polyphenols or vitamins. In this review, we summarize the existing in vitro, in vivo, and clin. data from published studies addressing the optimization of bioavailability of stilbenoids. Stilbenoids face low bioavailability due to their chem. structure. This can be improved by the use of novel drug delivery systems or enhancers, which are discussed in this review. Current in vitro and in vivo evidence suggests that both approaches are very promising and increase the absorption of the original substance by several times. However, data from more clin. trials are required.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisVKgsbfJ&md5=d50896a58827aad5b910f04bf650c699
21. 21

    Amri, A.; Chaumeil, J. C.; Sfar, S.; Charrueau, C. Administration of Resveratrol: What Formulation Solutions to Bioavailability Limitations?. J. Controlled Release 2012, 158 (2), 182– 193,  DOI: 10.1016/j.jconrel.2011.09.083

    Google Scholar

    21

    Administration of resveratrol: What formulation solutions to bioavailability limitations?

    Amri, A.; Chaumeil, J. C.; Sfar, S.; Charrueau, C.

    Journal of Controlled Release (2012), 158 (2), 182-193CODEN: JCREEC; ISSN:0168-3659. (Elsevier B.V.)

    A review. Resveratrol (3,5,4'-trihydroxystilbene), a naturally occurring polyphenol, has attracted considerable interest for its beneficial potentials for human health, which include anti-oxidant, anti-inflammatory, cardioprotective and anti-tumor activities. However, the in vivo biol. effects of resveratrol appear strongly limited by its low bioavailability, which is a barrier to the development of therapeutic applications. In this context, an increasing no. of recent studies have aimed at designing novel resveratrol formulations to overcome its poor soly., limited stability, high metabolization and weak bioavailability. This review outlines physicochem. and pharmacokinetic limitations to resveratrol bioavailability, describes formulations tested for resveratrol administration, controlled release and targeting, and identifies future opportunities for resveratrol delivery.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xjt1egsrY%253D&md5=61c6e485b255ad16367d8eddf3146b7d
22. 22

    Censi, R.; Di Martino, P. Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs. Molecules 2015, 20 (10), 18759– 18776,  DOI: 10.3390/molecules201018759

    Google Scholar

    22

    Polymorph impact on the bioavailability and stability of poorly soluble drugs

    Censi, Roberta; Di Martino, Piera

    Molecules (2015), 20 (10), 18759-18776CODEN: MOLEFW; ISSN:1420-3049. (MDPI AG)

    Drugs with low water soly. are predisposed to poor and variable oral bioavailability and, therefore, to variability in clin. response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhyd. and solvate/hydrate forms) may resolve these bioavailability problems, but they can be a challenge to ensure physicochem. stability for the entire shelf life of the drug product. Since clin. failures of polymorph drugs have not been uncommon, and some of them have been entirely unexpected, the Food and Drug Administration (FDA) and the International Conference on Harmonization (ICH) has required preliminary and exhaustive screening studies to identify and characterize all the polymorph crystal forms for each drug. In the past, the polymorphism of many drugs was detected fortuitously or through manual time consuming methods; today, drug crystal engineering, in particular, combinatorial chem. and high-throughput screening, makes it possible to easily and exhaustively identify stable polymorphic and/or hydrate/dehydrate forms of poorly sol. drugs, in order to overcome bioavailability related problems or clin. failures. This review describes the concepts involved, provides examples of drugs characterized by poor soly. for which polymorphism has proven important, outlines the state-of-the-art technologies and discusses the pertinent regulations.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslartb7I&md5=e290e2ebc06a16d1b6afe1b0d65b4c9a
23. 23

    Hošek, J.; Leláková, V.; Bobál, P.; Pížová, H.; Gazdová, M.; Malaník, M.; Jakubczyk, K.; Veselý, O.; Landa, P.; Temml, V.; Schuster, D.; Prachyawarakorn, V.; Pailee, P.; Ren, G.; Zpurný, F.; Oravec, M.; Šmejkal, K. Prenylated Stilbenoids Affect Inflammation by Inhibiting the NF-κB/AP-1 Signaling Pathway and Cyclooxygenases and Lipoxygenase. J. Nat. Prod 2019, 82 (7), 1839– 1848,  DOI: 10.1021/acs.jnatprod.9b00081

    Google Scholar

    23

    Prenylated Stilbenoids Affect Inflammation by Inhibiting the NF-κB/AP-1 Signaling Pathway and Cyclooxygenases and Lipoxygenase

    Hosek, Jan; Lelakova, Veronika; Bobal, Pavel; Pizova, Hana; Gazdova, Marketa; Malanik, Milan; Jakubczyk, Karolina; Vesely, Ondrej; Landa, Premysl; Temml, Veronika; Schuster, Daniela; Prachyawarakorn, Vilailak; Pailee, Phanruethai; Ren, Gang; Zpurny, Filip; Oravec, Michal; Smejkal, Karel

    Journal of Natural Products (2019), 82 (7), 1839-1848CODEN: JNPRDF; ISSN:0163-3864. (American Chemical Society-American Society of Pharmacognosy)

    Stilbenoids are important components of foods (e.g., peanuts, grapes, various edible berries), beverages (wine, white tea), and medicinal plants. Many publications have described the anti-inflammatory potential of stilbenoids, including the widely known trans-resveratrol and its analogs. However, very little information is available regarding the activity of their prenylated derivs. One new prenylated stilbenoid (2, I) was isolated from Artocarpus altilis and characterized structurally based on 1D and 2D NMR anal. and HR-MS. Three other prenylated stilbenoids were prepd. synthetically (9-11, II, III, IV). Their antiphlogistic potential was detd. by testing them together with known natural prenylated stilbenoids from Macaranga siamensis and Artocarpus heterophyllus in both cell-free and cell assays. The inhibition of 5-lipoxygenase (5-LOX) was also shown by simulated mol. docking for the most active stilbenoids in order to elucidate the mode of interaction between these compds. and the enzyme. Their effects on the pro-inflammatory nuclear factor-κB (NF-κB) and the activator protein 1 (AP-1) signaling pathway were also analyzed. The THP1-XBlue-MD2-CD14 cell line was used as a model for detg. their anti-inflammatory potential and LPS stimulation of Toll-like receptor 4 induced a signaling cascade leading to the activation of NF-κB/AP-1. The ability of prenylated stilbenoids to attenuate the prodn. of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was further evaluated using LPS-stimulated THP-1 macrophages.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXht1yrt7%252FJ&md5=7ca89a08481335b1079bf3da86d73c12
24. 24

    Leláková, V.; Béraud-Dufour, S.; Hošek, J.; Šmejkal, K.; Prachyawarakorn, V.; Pailee, P.; Widmann, C.; Václavík, J.; Coppola, T.; Mazella, J.; Blondeau, N.; Heurteaux, C. Therapeutic Potential of Prenylated Stilbenoid Macasiamenene F through Its Anti-Inflammatory and Cytoprotective Effects on LPS-Challenged Monocytes and Microglia. J. Ethnopharmacol. 2020, 263, 113147  DOI: 10.1016/j.jep.2020.113147

    Google Scholar

    24

    Therapeutic potential of prenylated stilbenoid macasiamenene F through its anti-inflammatory and cytoprotective effects on LPS-challenged monocytes and microglia

    Lelakova, Veronika; Beraud-Dufour, Sophie; Hosek, Jan; Smejkal, Karel; Prachyawarakorn, Vilailak; Pailee, Phanruethai; Widmann, Catherine; Vaclavik, Jiri; Coppola, Thierry; Mazella, Jean; Blondeau, Nicolas; Heurteaux, Catherine

    Journal of Ethnopharmacology (2020), 263 (), 113147CODEN: JOETD7; ISSN:0378-8741. (Elsevier Ireland Ltd.)

    Macaranga Thou.(Euphorbiaceae) is a large genus that comprises over 300 species distributed between Western Africa and the islands of the South Pacific. Plants of this genus have a long-standing history of use in traditional medicine for different purposes, including the treatment of inflammation. Fresh and dried leaves of certain Macaranga species (e.g. M. tanarius (L.) Mull.Arg.), have been used to treat cuts, bruises, boils, swellings, sores and covering of wounds in general. Several reports described Macaranga spp. being a rich source of polyphenols, such as prenylated stilbenoids and flavonoids, mostly responsible for its biol. activity. Similarly, an abundant content of prenylated stilbenes was also described in M. siamensis S.J. Davies, species recently identified (2001) in Thailand. While the resp. biol. activity of the prenylated stilbenes from M. siamensis was poorly investigated to date, our recent study pointed out the interest as the natural source of several novel anti-inflammatory stilbenoids isolated from this species. This work investigated the potential anti-inflammatory effects of the stilbenoid macasiamenene F (MF) isolated from M. siamensis S.J. Davies (Euphorbiaceae) on the lipopolysaccharide (LPS)-induced inflammation-like response of monocytes and microglia, major cells involved in the peripheral and central inflammatory response, resp. LPS-induced stimulation of TLR4 signaling led to the activation of inflammatory pathways in in vitro models of THP-1 and THP-1-XBlueTM-MD2-CD14 human monocytes, BV-2 mouse microglia, and an ex vivo model of brain-sorted mouse microglia. The ability of the stilbenoid MF to intervene in the IκB/NF-κB and MAPKs/AP-1 inflammatory cascade was investigated. The gene and protein expressions of the pro-inflammatory cytokines IL-1β and TNF-α were evaluated at the transcription and translation levels. The protective effect of MF against LPS-triggered microglial loss was assessed by cell counting and the LDH assay. MF demonstrated beneficial effects, reducing both monocyte and microglial inflammation as assessed in vitro. It efficiently inhibited the degrdn. of IκBα, thereby reducing the NF-κB activity and TNF-α expression in human monocytes. Furthermore, the LPS-induced expression of IL-1β and TNF-α in microglia was dampened by pre-, co-, or post-treatment with MF. In addn. to its anti-inflammatory effect, MF demonstrated a cytoprotective effect against the LPS-induced death of BV-2 microglia. Our research into anti-inflammatory and protective effects of MF has shown that it is a promising candidate for further in vitro and in vivo investigations of MF interventions with respect to acute and chronic inflammation, including potentially beneficial effects on the inflammatory component of brain diseases such as stroke and Alzheimer's disease.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs1eqs7%252FJ&md5=8b6bfc53691913a23eb1b4fc178bae90
25. 25

    Fukuta, T.; Ishii, T.; Asai, T.; Oku, N. Applications of Liposomal Drug Delivery Systems to Develop Neuroprotective Agents for the Treatment of Ischemic Stroke. Biol. Pharm. Bull. 2019, 42 (3), 319– 326,  DOI: 10.1248/bpb.b18-00683

    Google Scholar

    25

    Applications of liposomal drug delivery systems to develop neuroprotective agents for the treatment of ischemic stroke

    Fukuta, Tatsuya; Ishii, Takayuki; Asai, Tomohiro; Oku, Naoto

    Biological & Pharmaceutical Bulletin (2019), 42 (3), 319-326CODEN: BPBLEO; ISSN:0918-6158. (Pharmaceutical Society of Japan)

    A review. Ischemic stroke is one of the leading causes of severe disability and death. In clin. settings, tissue plasminogen activator (t-PA) for thrombolytic therapy is the only globally approved drug for the treatment of ischemic stroke. However, the proportion of patients who receive t-PA therapy is extremely limited due to its narrow therapeutic time window (TTW) and the risk of cerebral hemorrhage. Cerebral ischemia-reperfusion (I/R) injury is also a serious problem for patients' outcomes. Hence, the development of more effective therapies has been desired to prolong the TTW of t-PA and prevent cerebral I/R injury. For delivering drugs into the brain, the blood-brain barrier (BBB) must be overcome since it limits drug penetration into the brain, leading to insufficient therapeutic efficacy. As a distinctive pathol. after an ischemic stroke, it was reported that the vascular permeability of the BBB is increased around the ischemic region. We found that nano-sized liposomes can pass through the disrupted BBB and accumulate in the I/R region, and that delivery of neuroprotective agents using a liposomal drug delivery system (DDS) is effective for the treatment of cerebral I/R injury. Moreover, we have recently demonstrated that combination therapy with liposomal drugs and t-PA can suppress the deleterious effects of t-PA and extend its TTW in a rat ischemic stroke model. These findings indicate that applications of nanoparticle DDS technol. could be a hopeful approach to drug development for ischemic stroke therapy. In this review, we introduce our findings on ischemic stroke treatment using liposomal DDS and recent advances from other research groups.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsVKku7vL&md5=263e39ee55300e3c47cd101ccd8c1cd0
26. 26

    Montesinos, R. N. Liposomal Drug Delivery to the Central Nervous System; IntechOpen, 2017.

    Google Scholar

    There is no corresponding record for this reference.
27. 27

    Vieira, D. B.; Gamarra, L. F. Getting into the Brain: Liposome-Based Strategies for Effective Drug Delivery across the Blood–Brain Barrier. Int. J. Nanomed. 2016, 11, 5381– 5414,  DOI: 10.2147/IJN.S117210

    Google Scholar

    27

    Getting into the brain: liposome-based strategies for effective drug delivery across the blood-brain barrier

    Vieira, Debora B.; Gamarra, Lionel F.

    International Journal of Nanomedicine (2016), 11 (), 5381-5414CODEN: IJNNHQ; ISSN:1178-2013. (Dove Medical Press Ltd.)

    This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood-brain barrier. Due to their unique physicochem. characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurol. diseases, such as Alzheimer's, Parkinson's, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain. Covalent ligation of such macromols. as peptides, antibodies, and RNA aptamers is an effective method for receptor-targeting liposomes, which allows their blood-brain barrier penetration and/or the delivery of their therapeutic mol. specifically to the disease site. Addnl., methods have been employed for the development of liposomes that can respond to external stimuli. It can be concluded that the development of liposomes for brain delivery is still in its infancy, although these systems have the potential to revolutionize the ways in which medicine is administered.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXpt1yntQ%253D%253D&md5=1b0773df84edda742c2ca10bee7cc8ad
28. 28

    Fukuta, T.; Asai, T.; Sato, A.; Namba, M.; Yanagida, Y.; Kikuchi, T.; Koide, H.; Shimizu, K.; Oku, N. Neuroprotection against Cerebral Ischemia/Reperfusion Injury by Intravenous Administration of Liposomal Fasudil. Int. J. Pharm. 2016, 506 (1–2), 129– 137,  DOI: 10.1016/j.ijpharm.2016.04.046

    Google Scholar

    28

    Neuroprotection against cerebral ischemia/reperfusion injury by intravenous administration of liposomal fasudil

    Fukuta, Tatsuya; Asai, Tomohiro; Sato, Akihiko; Namba, Mio; Yanagida, Yosuke; Kikuchi, Takashi; Koide, Hiroyuki; Shimizu, Kosuke; Oku, Naoto

    International Journal of Pharmaceutics (Amsterdam, Netherlands) (2016), 506 (1-2), 129-137CODEN: IJPHDE; ISSN:0378-5173. (Elsevier B.V.)

    Fasudil, a Rho-kinase inhibitor, is a promising neuroprotectant against ischemic stroke; however, its low bioavailability is an obstacle to be overcome. Our previous study revealed that the liposomal drug delivery system is a hopeful strategy to increase the therapeutic efficacy of neuroprotectants. In the present study, the usefulness of i.v. administered liposomal fasudil for cerebral ischemia/reperfusion (I/R) injury treatment was examd. in transient middle cerebral artery occlusion (t-MCAO) rats. The results showed that PEGylated liposomes of approx. 100 nm in diam. accumulated more extensively in the I/R region compared with those of over 200 nm. Confocal images showed that fluorescence-labeled liposomal fasudil was widely distributed in the I/R region, and was not noticeably taken up by microglia, which are well-known resident macrophages in the brain, and neuronal cells. These data indicated that liposomal fasudil mainly exerted its pharmacol. activity by releasing fasudil from the liposomes in the I/R region. Moreover, liposomal fasudil effectively suppressed neutrophil invasion and brain cell damage in the t-MCAO rats, resulting in amelioration of their motor function deficits. These findings demonstrated both the importance of particle size for neuroprotectant delivery and the effectiveness of liposomal fasudil for the treatment of cerebral I/R injury.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XntVCrsLk%253D&md5=48abd44f7197eaea1ea7852725f0eb46
29. 29

    Fukuta, T.; Ishii, T.; Asai, T.; Sato, A.; Kikuchi, T.; Shimizu, K.; Minamino, T.; Oku, N. Treatment of Stroke with Liposomal Neuroprotective Agents under Cerebral Ischemia Conditions. Eur. J. Pharm. Biopharm. 2015, 97 (Pt A), 1– 7,  DOI: 10.1016/j.ejpb.2015.09.020

    Google Scholar

    29

    Treatment of stroke with liposomal neuroprotective agents under cerebral ischemia conditions

    Fukuta, Tatsuya; Ishii, Takayuki; Asai, Tomohiro; Sato, Akihiko; Kikuchi, Takashi; Shimizu, Kosuke; Minamino, Tetsuo; Oku, Naoto

    European Journal of Pharmaceutics and Biopharmaceutics (2015), 97 (Part_A), 1-7CODEN: EJPBEL; ISSN:0939-6411. (Elsevier B.V.)

    Since the proportion of patients given thrombolytic therapy with tissue plasminogen activator (t-PA) is very limited because of the narrow therapeutic window, the development of new therapies for ischemic stroke has been desired. We previously reported that liposomes injected i.v. accumulate in the ischemic region of the brain via disruption of the blood-brain barrier that occurs under cerebral ischemia. In the present study, we investigated the efficacy of a liposomal neuroprotective agent in middle cerebral artery occlusion (MCAO) rats to develop ischemic stroke therapy prior to the recovery of cerebral blood flow. For this purpose, PEGylated liposomes encapsulating FK506 (FK506-liposomes) were prepd. and injected i.v. into MCAO rats after a 1-h occlusion. This treatment significantly suppressed the expansion of oxidative stress and brain cell damage. In addn., administration of FK506-liposomes before reperfusion significantly ameliorated motor function deficits of the rats caused by ischemia/reperfusion injury. These findings suggest that FK506-liposomes effectively exerted a neuroprotective effect during ischemic conditions, and that combination therapy with a liposomal neuroprotectant plus t-PA could be a promising therapeutic strategy for ischemic stroke.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhs1aksLfP&md5=54fcdbf43437b8a5d92da5c1e5cc5772
30. 30

    Yoneda, S.; Fukuta, T.; Ozono, M.; Kogure, K. Enhancement of Cerebroprotective Effects of Lipid Nanoparticles Encapsulating FK506 on Cerebral Ischemia/Reperfusion Injury by Particle Size Regulation. Biochem. Biophys. Res. Commun. 2022, 611, 53– 59,  DOI: 10.1016/j.bbrc.2022.04.080

    Google Scholar

    30

    Enhancement of cerebroprotective effects of lipid nanoparticles encapsulating FK506 on cerebral ischemia/reperfusion injury by particle size regulation

    Yoneda, Shintaro; Fukuta, Tatsuya; Ozono, Mizune; Kogure, Kentaro

    Biochemical and Biophysical Research Communications (2022), 611 (), 53-59CODEN: BBRCA9; ISSN:0006-291X. (Elsevier B.V.)

    Delivery of cerebroprotective agents using liposomes has been demonstrated to be useful for treating cerebral ischemia/reperfusion (I/R) injury. We previously reported that i.v. administration of liposomes with diams. of 100 nm showed higher accumulation in the I/R region compared with larger liposomes (>200 nm) by passage through the disintegrated blood-brain barrier, suggesting a size-dependence for liposome-mediated drug delivery. Based on these findings, we hypothesized that regulation of liposomal particle size (<100 nm) may enhance the therapeutic efficacy of encapsulated drugs on cerebral I/R injury. Herein, we prepd. lipid nanoparticles (LNP) with particle sizes <100 nm by the microfluidics method and compared their therapeutic potential with LNP exhibiting sizes >100 nm in cerebral I/R model rats. I.v. administered smaller LNP (ca. 60 nm) exhibited wider accumulation and diffusivity in the brain parenchyma of the I/R region compared with larger LNP (>100 nm). Importantly, treatment with LNP encapsulating the cerebroprotective agent FK506 (FK-LNP) with particle sizes <100 nm showed greater cerebroprotective effects than FK-LNP with sizes >100 nm, and also significantly ameliorated brain injury. These results suggest that particle size regulation of LNP to sizes <100 nm can enhance the therapeutic effect of encapsulated drugs for treatment of cerebral I/R injury, and that FK-LNP could be a promising cerebroprotective agent.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhtVyhurfF&md5=516863818145b9e136305ea5ee6b1b84
31. 31

    Agrawal, M.; Ajazuddin; Tripathi, D. K.; Swarnlata, S.; Shailendra, S.; Antimisiaris, S. G.; Mourtas, S.; Hammarlund-Udenaes, M.; Alexander, A. Recent Advancements in Liposomes Targeting Strategies to Cross Blood-Brain Barrier (BBB) for the Treatment of Alzheimer’s Disease. J. Controlled Release 2017, 260, 61– 77,  DOI: 10.1016/j.jconrel.2017.05.019

    Google Scholar

    31

    Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer's disease

    Agrawal, Mukta; Ajazuddin; Tripathi, Dulal K.; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G.; Mourtas, Spyridon; Hammarlund-Udenaes, Margareta; Alexander, Amit

    Journal of Controlled Release (2017), 260 (), 61-77CODEN: JCREEC; ISSN:0168-3659. (Elsevier B.V.)

    A review. In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiol. barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug mols., various proteins and peptides, small hydrophilic mols., large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli. This functionally essential structure creates a major hurdle for delivery of any drug into the brain. Still, there are some provisions on BBB which facilitate the entry of useful substances in the brain via specific mechanisms like passive diffusion, receptor-mediated transcytosis, carrier-mediated transcytosis etc. Another important factor for drug transport is the selection of a suitable drug delivery systems like, liposome, which is a novel drug carrier system offering a potential approach to resolving this problem. Its unique phospholipid bilayer structure (similar to physiol. membrane) had made it more compatible with the lipoidal layer of BBB and helps the drug to enter the brain. The present review work focused on various surface modifications with functional ligand (like lactoferrin, transferrin etc.) and carrier mols. (such as glutathione, glucose etc.) on the liposomal structure to enhance its brain targeting ability towards the successful treatment of Alzheimer disease.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXosFWhtbk%253D&md5=7061cea9e498ebd82747e3bb47e8438d
32. 32

    Arias-Alpizar, G.; Kong, L.; Vlieg, R. C.; Rabe, A.; Papadopoulou, P.; Meijer, M. S.; Bonnet, S.; Vogel, S.; van Noort, J.; Kros, A.; Campbell, F. Light-Triggered Switching of Liposome Surface Charge Directs Delivery of Membrane Impermeable Payloads in Vivo. Nat. Commun. 2020, 11 (1), 3638  DOI: 10.1038/s41467-020-17360-9

    Google Scholar

    32

    Light-triggered switching of liposome surface charge directs delivery of membrane impermeable payloads in vivo

    Arias-Alpizar, Gabriela; Kong, Li; Vlieg, Redmar C.; Rabe, Alexander; Papadopoulou, Panagiota; Meijer, Michael S.; Bonnet, Sylvestre; Vogel, Stefan; van Noort, John; Kros, Alexander; Campbell, Frederick

    Nature Communications (2020), 11 (1), 3638CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)

    Surface charge plays a fundamental role in detg. the fate of a nanoparticle, and any encapsulated contents, in vivo. Herein, we describe, and visualise in real time, light-triggered switching of liposome surface charge, from neutral to cationic, in situ and in vivo (embryonic zebrafish). Prior to light activation, i.v. administered liposomes, composed of just two lipid reagents, freely circulate and successfully evade innate immune cells present in the fish. Upon in situ irradn. and surface charge switching, however, liposomes rapidly adsorb to, and are taken up by, endothelial cells and/or are phagocytosed by blood resident macrophages. Coupling complete external control of nanoparticle targeting together with the intracellular delivery of encapsulated (and membrane impermeable) cargos, these compositionally simple liposomes are proof that advanced nanoparticle function in vivo does not require increased design complexity but rather a thorough understanding of the fundamental nano-bio interactions involved.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVert7vM&md5=5c26e1033019df38a30ff09599a92c07
33. 33

    Suk, J. S.; Xu, Q.; Kim, N.; Hanes, J.; Ensign, L. M. PEGylation as a Strategy for Improving Nanoparticle-Based Drug and Gene Delivery. Adv. Drug Delivery Rev. 2016, 99 (Pt A), 28– 51,  DOI: 10.1016/j.addr.2015.09.012

    Google Scholar

    33

    PEGylation as a strategy for improving nanoparticle-based drug and gene delivery

    Suk, Jung Soo; Xu, Qingguo; Kim, Namho; Hanes, Justin; Ensign, Laura M.

    Advanced Drug Delivery Reviews (2016), 99 (Part_A), 28-51CODEN: ADDREP; ISSN:0169-409X. (Elsevier B.V.)

    Coating the surface of nanoparticles with polyethylene glycol (PEG), or "PEGylation", is a commonly used approach for improving the efficiency of drug and gene delivery to target cells and tissues. Building from the success of PEGylating proteins to improve systemic circulation time and decrease immunogenicity, the impact of PEG coatings on the fate of systemically administered nanoparticle formulations has, and continues to be, widely studied. PEG coatings on nanoparticles shield the surface from aggregation, opsonization, and phagocytosis, prolonging systemic circulation time. Here, we briefly describe the history of the development of PEGylated nanoparticle formulations for systemic administration, including how factors such as PEG mol. wt., PEG surface d., nanoparticle core properties, and repeated administration impact circulation time. A less frequently discussed topic, we then describe how PEG coatings on nanoparticles have also been utilized for overcoming various biol. barriers to efficient drug and gene delivery assocd. with other modes of administration, ranging from gastrointestinal to ocular. Finally, we describe both methods for PEGylating nanoparticles and methods for characterizing PEG surface d., a key factor in the effectiveness of the PEG surface coating for improving drug and gene delivery.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhs1CqurrP&md5=fecfbdedd72ee97571c913a9ac3cd93f
34. 34

    Koudelka, Š.; Turánek-Knötigová, P.; Mašek, J.; Korvasová, Z.; Škrabalová, M.; Plocková, J.; Bartheldyová, E.; Turánek, J. Liposomes with High Encapsulation Capacity for Paclitaxel: Preparation, Characterisation and in Vivo Anticancer Effect. J. Pharm. Sci. 2010, 99 (5), 2309– 2319,  DOI: 10.1002/jps.21992

    Google Scholar

    34

    Liposomes with high encapsulation capacity for paclitaxel: Preparation, characterisation and in vivo anticancer effect

    Koudelka, Stepan; Turanek-Knoetigova, Pavlina; Masek, Josef; Korvasova, Zina; Skrabalova, Michaela; Plockova, Jana; Bartheldyova, Eliska; Turanek, Jaroslav

    Journal of Pharmaceutical Sciences (2010), 99 (5), 2309-2319CODEN: JPMSAE; ISSN:0022-3549. (Wiley-Liss, Inc.)

    Paclitaxel (PTX) is approved for the treatment of ovarian and breast cancer. The com. available prepn. of PTX, Cremophor EL is assocd. with hypersensitivity reactions in spite of a suitable premedication. In general, the developed liposomal PTX formulations are troubled with low PTX encapsulation capacity (maximal content, 3 mol%) and accompanied by PTX crystn. The application of "pocket-forming" lipids significantly increased the encapsulation capacity of PTX in the liposomes up to 10 mol%. Stable lyophilised prepn. of PTX (7 mol%) encapsulated in the liposomes composed of SOPC/POPG/MOPC (molar ratio, 60:20:20) doped with 5 mol% vitamin E had the size distribution of 180-190 nm (PDI, 0.1) with ζ-potential of -31 mV. Sucrose was found to be a suitable cryoprotectant at the lipid:sugar molar ratios of 1:5-1:10. This liposomal formulation did not show any evidence of toxicity in C57BL/6 mice treated with the highest doses of PTX (100 mg/kg administered as a single dose and 150 mg/kg as a cumulative dose applied in three equiv. doses in 48-h intervals). A dose-dependent anticancer effect was found in both hollow fiber implants and syngenic B16F10 melanoma mouse tumor models. © 2009 Wiley-Liss, Inc. and the American Pharmacists Assocn. J Pharm Sci 99: 2309-2319, 2010.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjt1ahu7w%253D&md5=24f888880c20df2bb9b854afa2c6df71
35. 35

    Šimečková, P.; Hubatka, F.; Kotouček, J.; Turánek Knötigová, P.; Mašek, J.; Slavík, J.; Kováč, O.; Neča, J.; Kulich, P.; Hrebík, D.; Stráská, J.; Pěnčíková, K.; Procházková, J.; Diviš, P.; Macaulay, S.; Mikulík, R.; Raška, M.; Machala, M.; Turánek, J. Gadolinium Labelled Nanoliposomes as the Platform for MRI Theranostics: In Vitro Safety Study in Liver Cells and Macrophages. Sci. Rep. 2020, 10 (1), 4780  DOI: 10.1038/s41598-020-60284-z

    Google Scholar

    35

    Gadolinium labelled nanoliposomes as the platform for MRI theranostics: in vitro safety study in liver cells and macrophages

    Simeckova, Pavlina; Hubatka, Frantisek; Kotoucek, Jan; Turanek Knotigova, Pavlina; Masek, Josef; Slavik, Josef; Kovac, Ondrej; Neca, Jiri; Kulich, Pavel; Hrebik, Dominik; Straska, Jana; Pencikova, Katerina; Prochazkova, Jirina; Divis, Pavel; Macaulay, Stuart; Mikulik, Robert; Raska, Milan; Machala, Miroslav; Turanek, Jaroslav

    Scientific Reports (2020), 10 (1), 4780CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)

    Gadolinium (Gd)-based contrast agents are extensively used for magnetic resonance imaging (MRI). Liposomes are potential nanocarrier-based biocompatible platforms for development of new generations of MRI diagnostics. Liposomes with Gd-complexes (Gd-lip) co-encapsulated with thrombolytic agents can serve both for imaging and treatment of various pathol. states including stroke. In this study, we evaluated nanosafety of Gd-lip contg. PE-DTPA chelating Gd+3 prepd. by lipid film hydration method. We detected no cytotoxicity of Gd-lip in human liver cells including cancer HepG2, progenitor (non-differentiated) HepaRG, and differentiated HepaRG cells. Furthermore, no potential side effects of Gd-lip were found using a complex system including general biomarkers of toxicity, such as induction of early response genes, oxidative, heat shock and endoplasmic reticulum stress, DNA damage responses, induction of xenobiotic metabolizing enzymes, and changes in sphingolipid metab. in differentiated HepaRG. Moreover, Gd-lip did not show pro-inflammatory effects, as assessed in an assay based on activation of inflammasome NLRP3 in a model of human macrophages, and release of eicosanoids from HepaRG cells. In conclusion, this in vitro study indicates potential in vivo safety of Gd-lip with respect to hepatotoxicity and immunopathol. caused by inflammation.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlvFCnurw%253D&md5=bcd3a780b392c0e223463037e7f0d2d9
36. 36

    Coimbra, M.; Isacchi, B.; van Bloois, L.; Torano, J. S.; Ket, A.; Wu, X.; Broere, F.; Metselaar, J. M.; Rijcken, C. J. F.; Storm, G.; Bilia, R.; Schiffelers, R. M. Improving Solubility and Chemical Stability of Natural Compounds for Medicinal Use by Incorporation into Liposomes. Int. J. Pharm. 2011, 416 (2), 433– 442,  DOI: 10.1016/j.ijpharm.2011.01.056

    Google Scholar

    36

    Improving solubility and chemical stability of natural compounds for medicinal use by incorporation into liposomes

    Coimbra, Maria; Isacchi, Benedetta; van Bloois, Louis; Torano, Javier Sastre; Ket, Aldo; Wu, Xiaojie; Broere, Femke; Metselaar, Josbert M.; Rijcken, Cristianne J. F.; Storm, Gert; Bilia, Rita; Schiffelers, Raymond M.

    International Journal of Pharmaceutics (2011), 416 (2), 433-442CODEN: IJPHDE; ISSN:0378-5173. (Elsevier B.V.)

    Natural bioactive compds. have been studied for a long time for their chemopreventive and therapeutic potential in several chronic inflammatory diseases, including cancer. However, their physicochem. properties generally result in poor chem. stability and lack of in vivo bioavailability. Very few human clin. trials have addressed absorption, distribution, metab., and excretion of these compds. in relation to efficacy. This limits the use of these valuable natural compds. in the clinic. In this study, we examd. caffeic acid (derivs.), carvacrol (derivs.), thymol, pterostilbene (derivs.), and N-(3-oxo-dodecanoyl)-l-homoserine lactone. These are natural compds. with strong anti-inflammatory properties derived from plants and bacteria. However, these compds. have poor water soly. or are chem. unstable. To overcome these limitations we have prepd. liposomal formulations. Our results show that lipophilic 3-oxo-C12-homoserine lactone and stilbene derivs. can be loaded into liposomal lipid bilayer with efficiencies of 50-70%. Thereby, the liposomes solubilize these compds., allowing i.v. administration without use of solvents. When compds. could not be loaded into the lipid bilayer (carvacrol and thymol) or are rapidly extd. from the liposomes in the presence of serum albumin (3-oxo-C12-homoserine lactone and pterostilbene derivs.), derivatization of the compd. into a water-sol. prodrug was shown to improve loading efficiency and encapsulation stability. The phosphate forms of carvacrol and pterostilbene were loaded into the aq. interior of the liposomes and encapsulation was unaffected by the presence of serum albumin. Chem. instability of resveratrol was improved by liposome-encapsulation, preventing inactivating cis-trans isomerization. For caffeic acid, liposomal encapsulation did not prevent oxidn. into a variety of products. Still, by derivatization into a Ph ester, the compd. could be stably encapsulated without chem. degrdn. Despite the instability of liposome-assocn. of 3-oxo-C12-homoserine lactone and resveratrol, i.v. administration of these compds. inhibited tumor growth for approx. 70% in a murine tumor model, showing that simple solubilization can have important therapeutic benefits.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtVSqsLnF&md5=764e35885df7ac75e0d13068e4ab7ca2
37. 37

    Beaumont, P.; Faure, C.; Courtois, A.; Jourdes, M.; Marchal, A.; Teissedre, P.-L.; Richard, T.; Atgié, C.; Krisa, S. Trans-ε-Viniferin Encapsulation in Multi-Lamellar Liposomes: Consequences on Pharmacokinetic Parameters, Biodistribution and Glucuronide Formation in Rats. Nutrients 2021, 13 (12), 4212,  DOI: 10.3390/nu13124212

    Google Scholar

    37

    Trans-ε-Viniferin Encapsulation in Multi-Lamellar Liposomes: Consequences on Pharmacokinetic Parameters, Biodistribution and Glucuronide Formation in Rats

    Beaumont, Pauline; Faure, Chrystel; Courtois, Arnaud; Jourdes, Michael; Marchal, Axel; Teissedre, Pierre-Louis; Richard, Tristan; Atgie, Claude; Krisa, Stephanie

    Nutrients (2021), 13 (12), 4212CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)

    Trans-ε-viniferin (εVin) is a resveratrol dimer exhibiting promising biol. activities for human health. Its bioavailability being low, the development of encapsulation methods would be used to overcome this issue. The aim of this study was to measure the consequences of the encapsulation of εVin in multilamellar liposomes on its pharmacokinetic parameters, metab. and tissue distribution in rats. After oral administration of εVin (20 mg/kg body wt.), either as free or encapsulated forms, plasmas were sequentially collected (from 0 to 4 h) as well as liver, kidneys and adipose tissues (4 h after administration) and analyzed by LC-HRMS. The glucuronide metabolites (εVG) were also produced by hemisynthesis for their quantification in plasma and tissues. The encapsulation process did not significantly modify the pharmacokinetic parameters of εVin itself. However, a significant increase of the T1/2 was noticed for εVG after administration of the encapsulated form as compared to the free form. An accumulation of εVin and εVG in adipose tissues was noticed, and interestingly a significant increase of the latter in the mesenteric one after administration of the encapsulated form was highlighted. Since adipose tissues could represent storage depots, and encapsulation allows for prolonging the exposure time of glucuronide metabolites in the organism, this could be of interest to promote their potential biol. activities.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xht1arsLY%253D&md5=07633e548b94c926a119a60601d5f13f
38. 38

    Danaei, M.; Dehghankhold, M.; Ataei, S.; Hasanzadeh Davarani, F.; Javanmard, R.; Dokhani, A.; Khorasani, S.; Mozafari, M. R. Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics 2018, 10 (2), 57  DOI: 10.3390/pharmaceutics10020057

    Google Scholar

    38

    Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems

    Danaei, M.; Dehghankhold, M.; Ataei, S.; Davarani, F. Hasanzadeh; Javanmard, R.; Dokhani, A.; Khorasani, S.; Mozafari, M. R.

    Pharmaceutics (2018), 10 (2), 57/1-57/17CODEN: PHARK5; ISSN:1999-4923. (MDPI AG)

    Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-sol. drugs. They have the ability to incorporate both lipophilic and hydrophilic mols. and protecting them against degrdn. in vitro and in vivo. There is a no. of phys. attributes of lipid-based nanocarriers that det. their safety, stability, efficacy, as well as their in vitro and in vivo behavior. These include av. particle size/diam. and the polydispersity index (PDI), which is an indication of their quality with respect to the size distribution. The suitability of nanocarrier formulations for a particular route of drug administration depends on their av. diam., PDI and size stability, among other parameters. Controlling and validating these parameters are of key importance for the effective clin. applications of nanocarrier formulations. This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications. Liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes and tocosomes are presented as frequently-used lipidic drug carriers. The advantages and limitations of a range of available anal. techniques used to characterize lipidic nanocarrier formulations are also covered.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsVyktb7K&md5=6e7512d42f5c75d5fadfe955303471b2
39. 39

    Filippov, S. K.; Khusnutdinov, R.; Murmiliuk, A.; Inam, W.; Zakharova, L. Y.; Zhang, H.; Khutoryanskiy, V. V. Dynamic Light Scattering and Transmission Electron Microscopy in Drug Delivery: A Roadmap for Correct Characterization of Nanoparticles and Interpretation of Results. Mater. Horiz. 2023, 10 (12), 5354– 5370,  DOI: 10.1039/D3MH00717K

    Google Scholar

    39

    Dynamic light scattering and transmission electron microscopy in drug delivery: a roadmap for correct characterization of nanoparticles and interpretation of results

    Filippov, Sergey K.; Khusnutdinov, Ramil; Murmiliuk, Anastasiia; Inam, Wali; Zakharova, Lucia Ya.; Zhang, Hongbo; Khutoryanskiy, Vitaliy V.

    Materials Horizons (2023), 10 (12), 5354-5370CODEN: MHAOBM; ISSN:2051-6355. (Royal Society of Chemistry)

    A review. In this focus article, we provide a scrutinizing anal. of transmission electron microscopy (TEM) and dynamic light scattering (DLS) as the two common methods to study the sizes of nanoparticles with focus on the application in pharmaceutics and drug delivery. Control over the size and shape of nanoparticles is one of the key factors for many biomedical systems. Particle size will substantially affect their permeation through biol. membranes. For example, an enhanced permeation and retention effect requires a very narrow range of sizes of nanoparticles (50-200 nm) and even a minor deviation from these values will substantially affect the delivery of drug nanocarriers to the tumor. However, amazingly a great no. of research papers in pharmaceutics and drug delivery report a striking difference in nanoparticle size measured by the two most popular exptl. techniques (TEM and DLS). In some cases, this difference was reported to be 200-300%, raising the question of which size measurement result is more trustworthy. In this focus article, we primarily focus on the phys. aspects that are responsible for the routinely obsd. mismatch between TEM and DLS results. Some of these factors such as concn. and angle dependencies are commonly underestimated and misinterpreted. We convincingly show that correctly used exptl. procedures and a thorough anal. of results generated using both methods can eliminate the DLS and TEM data mismatch completely or will make the results much closer to each other. Also, we provide a clear roadmap for drug delivery and pharmaceutical researchers to conduct reliable DLS measurements.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXitVyksLvO&md5=71339241df970726c281e7016a0837b7
40. 40

    Bellow, S.; Latouche, G.; Brown, S. C.; Poutaraud, A.; Cerovic, Z. G. In Vivo Localization at the Cellular Level of Stilbene Fluorescence Induced by Plasmopara Viticola in Grapevine Leaves. J. Exp. Bot. 2012, 63 (10), 3697– 3707,  DOI: 10.1093/jxb/ers060

    Google Scholar

    40

    In vivo localization at the cellular level of stilbene fluorescence induced by Plasmopara viticola in grapevine leaves

    Bellow, Sebastien; Latouche, Gwendal; Brown, Spencer C.; Poutaraud, Anne; Cerovic, Zoran G.

    Journal of Experimental Botany (2012), 63 (10), 3697-3707CODEN: JEBOA6; ISSN:0022-0957. (Oxford University Press)

    Accurate localization of phytoalexins is a key for better understanding their role. This work aims to localize stilbenes, the main phytoalexins of grapevine. The cellular localization of stilbene fluorescence induced by Plasmopara viticola, the agent of downy mildew, was detd. in grapevine leaves of very susceptible, susceptible, and partially resistant genotypes during infection. Laser scanning confocal microscopy and microspectrofluorimetry were used to acquire UV-excited autofluorescence three-dimensional images and spectra of grapevine leaves 5-6 days after inoculation. This noninvasive technique of investigation in vivo was completed with in vitro spectrofluorimetric studies on pure stilbenes as their fluorescence is largely affected by the physicochem. environment in various leaf compartments. Viscosity was the major physicochem. factor influencing stilbene fluorescence intensity, modifying fluorescence yield by more than two orders of magnitude. Striking differences in the localization of stilbene fluorescence induced by P. viticola were obsd. between the different genotypes. All inoculated genotypes displayed stilbene fluorescence in cell walls of guard cells and periclinal cell walls of epidermal cells. Higher fluorescence intensity was obsd. in guard-cell walls than in any other compartment due to increased local viscosity. In addn. stilbene fluorescence was found in epidermal cell vacuoles of the susceptible genotype and in the infected spongy parenchyma of the partially resistant genotype. The very susceptible genotype was devoid of fluorescence both in the epidermal vacuoles and the mesophyll. This strongly suggests that the resistance of grapevine leaves to P. viticola is correlated with the pattern of localization of induced stilbenes in host tissues.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVShtL7F&md5=9e921a1c9799b11625e61891026145ac
41. 41

    Cadena, P. G.; Pereira, M. A.; Cordeiro, R. B. S.; Cavalcanti, I. M. F.; Barros Neto, B.; Pimentel, M. do C. C. B.; Lima Filho, J. L.; Silva, V. L.; Santos-Magalhães, N. S. Nanoencapsulation of Quercetin and Resveratrol into Elastic Liposomes. Biochim. Biophys. Acta 2013, 1828 (2), 309– 316,  DOI: 10.1016/j.bbamem.2012.10.022

    Google Scholar

    41

    Nanoencapsulation of quercetin and resveratrol into elastic liposomes

    Cadena, Pabyton G.; Pereira, Marcela A.; Cordeiro, Rafaela B. S.; Cavalcanti, Isabella M. F.; Barros Neto, Benicio; Pimentel, Maria do Carmo C. B.; Lima Filho, Jose Luiz; Silva, Valdinete L.; Santos-Magalhaes, Nereide S.

    Biochimica et Biophysica Acta, Biomembranes (2013), 1828 (2), 309-316CODEN: BBBMBS; ISSN:0005-2736. (Elsevier B.V.)

    Based on the fact that quercetin (QUE) and resveratrol (RES) induce a synergic inhibition of the adipogenesis and increase apoptosis in adipocytes, and that sodium deoxycholate (SDC) has necrotic effects, the nanoencapsulation of QUE and RES into SDC-elastic liposomes is proposed as a new approach for dissolving the s.c. fat. The concn. of constituents and the effect of the drug incorporation into cyclodextrin inclusion complexes on the stability of QUE/RES-loaded liposomes were studied. The best liposomal formulation reduced the use of phosphatidylcholine and cholesterol in 17.7% and 68.4%, resp. Liposomes presented a mean diam. of 149 nm with a polydispersion index of 0.3. The zeta potential of liposomes was slightly neg. (- 13.3 mV) due to the presence of SDC in the phospholipid bilayer. Encapsulation efficiency of QUE and RES into liposomes was almost 97%. To summarize, QUE/RES-loaded elastic liposomes are stable and suitable for s.c. injection, thereby providing a new strategy for reducing s.c. fat.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVymsw%253D%253D&md5=450b749e9e80a479c9741a5eab225825
42. 42

    Pecyna, P.; Wargula, J.; Murias, M.; Kucinska, M. More Than Resveratrol: New Insights into Stilbene-Based Compounds. Biomolecules 2020, 10 (8), 1111,  DOI: 10.3390/biom10081111

    Google Scholar

    42

    More than resveratrol: new insights into stilbene-based compounds

    Pecyna, Paulina; Wargula, Joanna; Murias, Marek; Kucinska, Malgorzata

    Biomolecules (2020), 10 (8), 1111CODEN: BIOMHC; ISSN:2218-273X. (MDPI AG)

    A review. The concept of a scaffold concerns many aspects at different steps on the drug development path. In medicinal chem., the choice of relevant "drug-likeness" scaffold is a starting point for the design of the structure dedicated to specific mol. targets. For many years, the chem. uniqueness of the stilbene structure has inspired scientists from different fields such as chem., biol., pharmacy, and medicine. In this review, we present the outstanding potential of the stilbene-based derivs. Naturally occurring stilbenes, together with powerful synthetic chem. possibilities, may offer an excellent approach for discovering new structures and identifying their therapeutic targets. With the development of scientific tools, sophisticated equipment, and a better understanding of the disease pathogenesis at the mol. level, the stilbene scaffold has moved innovation in science. This paper mainly focuses on the stilbene-based compdounds beyond resveratrol, which are particularly attractive due to their biol. activity. Given the "fresh outlook" about different stilbene-based compdounds starting from stilbenoids with particular regard to isorhapontigenin and methoxy- and hydroxyl- analogs, the update about the combretastatins, and the very often overlooked and underestimated benzanilide analogs, we present a new story about this remarkable structure.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs1yjurnO&md5=1f82559c8be06d55b8fc847c0c36fc44
43. 43

    Zhou, T.; Jiang, Y.; Zeng, B.; Yang, B. The Cancer Preventive Activity and Mechanisms of Prenylated Resveratrol and Derivatives. Curr. Res. Toxicol. 2023, 5, 100113  DOI: 10.1016/j.crtox.2023.100113

    Google Scholar

    43

    The cancer preventive activity and mechanisms of prenylated resveratrol and derivatives

    Zhou Ting; Jiang Yueming; Yang Bao; Zhou Ting; Jiang Yueming; Yang Bao; Zhou Ting; Jiang Yueming; Yang Bao; Zeng Bin

    Current research in toxicology (2023), 5 (), 100113 ISSN:.

    Resveratrol is regarded as neutraceuticals with multiple health benefits. The introduction of prenyl can enhance the bioactivity. In this work, the cancer preventive activities and mechanisms of 18 prenylated reseveratrol and derivatives were investigated. The results showed that prenyl increased the antiproliferative activities of resveratrol, oxyresveratrol and piceatannol against cancer cells, and their antiproliferative activities were time- and dose-dependent. 4-C-prenylation was important for the antiproliferative activity of stilbenoids. The 4-C-prenyl stilbenoids showed better antiproliferative activities than other prenylated stilbenoids. 4-C-prenyl piceatannol showed the best antiproliferative activity. Human hepatoellular carcinomas (HepG2) cell was more sensitive to prenylated stilbenoids than human MCF-7 breast carcinoma cell. 4-C-prenyl piceatannol had high affinities to Caspase-3, Caspase-9, CDK2 and Cyclin A2. The possible amino acids involved in binding 4-C-prenyl piceatannol were revealed. The expression of Caspase-3 and Caspase-9 were upregulated by 4-C-prenyl piceatannol and the expression of CDK2 and Cyclin A2 in HepG2 cells were downregulated, which contributed to apoptosis. The above results eludicated the possible antiproliferative mechanisms of prenylated stilbenoids.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2srmsl2quw%253D%253D&md5=af3c8ae25ac63e65b1973b3fc6634417
44. 44

    Yang, S.-C.; Tseng, C.-H.; Wang, P.-W.; Lu, P.-L.; Weng, Y.-H.; Yen, F.-L.; Fang, J.-Y. Pterostilbene, a Methoxylated Resveratrol Derivative, Efficiently Eradicates Planktonic, Biofilm, and Intracellular MRSA by Topical Application. Front. Microbiol. 2017, 8, 1103,  DOI: 10.3389/fmicb.2017.01103

    Google Scholar

    44

    Pterostilbene, a Methoxylated Resveratrol Derivative, Efficiently Eradicates Planktonic, Biofilm, and Intracellular MRSA by Topical Application

    Yang Shih-Chun; Weng Yi-Han; Fang Jia-You; Tseng Chih-Hua; Tseng Chih-Hua; Tseng Chih-Hua; Tseng Chih-Hua; Yen Feng-Lin; Wang Pei-Wen; Lu Po-Liang; Lu Po-Liang; Yen Feng-Lin; Fang Jia-You; Fang Jia-You

    Frontiers in microbiology (2017), 8 (), 1103 ISSN:1664-302X.

    Pterostilbene is a methoxylated derivative of resveratrol originated from natural sources. We investigated the antibacterial activity of pterostilbene against drug-resistant Staphylococcus aureus and the feasibility of using it to treat cutaneous bacteria. The antimicrobial effect was evaluated using an in vitro culture model and an in vivo mouse model of cutaneous infection. The minimum inhibitory concentration (MIC) assay demonstrated a superior biocidal activity of pterostilbene compared to resveratrol (8~16-fold) against methicillin-resistant S. aureus (MRSA) and clinically isolated vancomycin-intermediate S. aureus (VISA). Pterostilbene was found to reduce MRSA biofilm thickness from 18 to 10 μm as detected by confocal microscopy. Pterostilbene showed minimal toxicity to THP-1 cells and was readily engulfed by the macrophages, facilitating the eradication of intracellular MRSA. Pterostilbene exhibited increased skin absorption over resveratrol by 6-fold. Topical pterostilbene application improved the abscess formation produced by MRSA by reducing the bacterial burden and ameliorating the skin architecture. The potent anti-MRSA capability of pterostilbene was related to bacterial membrane leakage, chaperone protein downregulation, and ribosomal protein upregulation. This mechanism of action was different from that of resveratrol according to proteomic analysis and molecular docking. Pterostilbene has the potential to serve as a novel class of topically applied agents for treating MRSA infection in the skin while demonstrating less toxicity to mammalian cells.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cjivVSisw%253D%253D&md5=cd651174dbd934a54e9789d0f9ed5d21
45. 45

    Leláková, V. Evaluation of the Influence of Selected Stilbenes on Neuroprotection against Stroke with a Focus on Inflammatory Signaling, Doctoral Dissertation; Université Côte d’Azur: Nice, France; Masaryk University: Brno, Czech Republic, 2020.

    Google Scholar

    There is no corresponding record for this reference.
46. 46

    Chang, C.-C.; Liu, D.-Z.; Lin, S.-Y.; Liang, H.-J.; Hou, W.-C.; Huang, W.-J.; Chang, C.-H.; Ho, F.-M.; Liang, Y.-C. Liposome Encapsulation Reduces Cantharidin Toxicity. Food Chem. Toxicol. 2008, 46 (9), 3116– 3121,  DOI: 10.1016/j.fct.2008.06.084

    Google Scholar

    46

    Liposome encapsulation reduces cantharidin toxicity

    Chang, Chun-Chao; Liu, Der-Zen; Lin, Shyr-Yi; Liang, Hong-Jen; Hou, Wen-Chi; Huang, Wei-Jan; Chang, Chih-Hsiang; Ho, Feng-Ming; Liang, Yu-Chih

    Food and Chemical Toxicology (2008), 46 (9), 3116-3121CODEN: FCTOD7; ISSN:0278-6915. (Elsevier Ltd.)

    Several reports have demonstrated that cantharidin is a strong anticancer compd. in vitro; however, its in vivo usefulness is often limited due to its high systemic toxicity. Cantharidin was encapsulated into pegylated liposomes and studied its activity against human breast cancer MCF-7 cells in vitro and its systemic toxicity in mice. Another two methods were also used to reduce the dosage of cantharidin, including labeling liposomal cantharidin with octreotide and exposing cells to hyperbaric oxygen. The cytotoxic activity of pegylated liposomal cantharidin was drastically reduced compared with free cantharidin in vitro. Octreotide-labeled pegylated liposomal cantharidin induced cell death by specifically targeting somatostatin receptors in MCF-7 cells. Cell death was augmented with a low dose of cantharidin under hyperbaric oxygen. Liposomal cantharidin had significantly less systemic toxicity than free cantharidin in vivo and also exhibited a high efficacy against antitumor growth in nude mice. Thus, systemic toxicity of cantharidin can be mitigated by liposome encapsulation; however, that did not decrease its antitumor activity.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhtVKnsbjK&md5=8f4d44f0f5f5b8e07561be7192200889
47. 47

    Pailee, P.; Sangpetsiripan, S.; Mahidol, C.; Ruchirawat, S.; Prachyawarakorn, V. Cytotoxic and Cancer Chemopreventive Properties of Prenylated Stilbenoids from Macaranga Siamensis. Tetrahedron 2015, 71 (34), 5562– 5571,  DOI: 10.1016/j.tet.2015.06.058

    Google Scholar

    47

    Cytotoxic and cancer chemopreventive properties of prenylated stilbenoids from Macaranga siamensis

    Pailee, Phanruethai; Sangpetsiripan, Suwannee; Mahidol, Chulabhorn; Ruchirawat, Somsak; Prachyawarakorn, Vilailak

    Tetrahedron (2015), 71 (34), 5562-5571CODEN: TETRAB; ISSN:0040-4020. (Elsevier Ltd.)

    Twenty-five new compds., including macasiamenenes A-U (1-21), a macasiamenin A (22), a macasiamenone A (23), and two macasiamenols A and B (24 and 25), together with five known compds. (26-30) were isolated from the dichloromethane ext. of the leaves and twigs of Macaranga siamensis. Their structures were established using spectroscopic techniques. Their cytotoxic and antioxidant properties were evaluated together with their effectiveness as aromatase inhibitors.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtVOhtb7N&md5=62ec06681c1ad9385964c3764dbc9749
48. 48

    Kuronuma, K.; Mitsuzawa, H.; Takeda, K.; Nishitani, C.; Chan, E. D.; Kuroki, Y.; Nakamura, M.; Voelker, D. R. Anionic Pulmonary Surfactant Phospholipids Inhibit Inflammatory Responses from Alveolar Macrophages and U937 Cells by Binding the Lipopolysaccharide-Interacting Proteins CD14 and MD-2. J. Biol. Chem. 2009, 284 (38), 25488– 25500,  DOI: 10.1074/jbc.M109.040832

    Google Scholar

    48

    Anionic Pulmonary Surfactant Phospholipids Inhibit Inflammatory Responses from Alveolar Macrophages and U937 Cells by Binding the Lipopolysaccharide-interacting Proteins CD14 and MD-2

    Kuronuma, Koji; Mitsuzawa, Hiroaki; Takeda, Katsuyuki; Nishitani, Chiaki; Chan, Edward D.; Kuroki, Yoshio; Nakamura, Mari; Voelker, Dennis R.

    Journal of Biological Chemistry (2009), 284 (38), 25488-25500CODEN: JBCHA3; ISSN:0021-9258. (American Society for Biochemistry and Molecular Biology)

    Lipopolysaccharide (LPS), derived from Gram-neg. bacteria, is a major cause of acute lung injury and respiratory distress syndrome. Pulmonary surfactant is secreted as a complex mixt. of lipids and proteins onto the alveolar surface of the lung. Surfactant phospholipids are essential in reducing surface tension at the air-liq. interface and preventing alveolar collapse at the end of the respiratory cycle. In the present study, we detd. that palmitoyl-oleoylphosphatidylglycerol and phosphatidylinositol, which are minor components of pulmonary surfactant, and synthetic dimyristoylphosphatidylglycerol regulated the inflammatory response of alveolar macrophages. The anionic lipids significantly inhibited LPS-induced nitric oxide and tumor necrosis factor-α prodn. from rat and human alveolar macrophages and a U937 cell line by reducing the LPS-elicited phosphorylation of multiple intracellular protein kinases. The anionic lipids were also effective at attenuating inflammation when administered intratracheally to mice challenged with LPS. Binding studies revealed high affinity interactions between the palmitoyl-oleoylphosphatidylglycerol and the Toll-like receptor 4-interacting proteins CD14 and MD-2. Our data clearly identify important anti-inflammatory properties of the minor surfactant phospholipids at the environmental interface of the lung.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtFWhsbrO&md5=942511c6bf137355bba406a496c2cd67
49. 49

    Numata, M.; Voelker, D. R. ′Inflammatory and Anti-Viral Actions of Anionic Pulmonary Surfactant Phospholipids. Biochim. Biophys. Acta 2022, 1867 (6), 159139  DOI: 10.1016/j.bbalip.2022.159139

    Google Scholar

    49

    Anti-inflammatory and anti-viral actions of anionic pulmonary surfactant phospholipids

    Numata, Mari; Voelker, Dennis R.

    Biochimica et Biophysica Acta, Molecular and Cell Biology of Lipids (2022), 1867 (6), 159139CODEN: BBMLFG; ISSN:1388-1981. (Elsevier B.V.)

    A review. Pulmonary surfactant is a mixt. of lipids and proteins, consisting of 90% phospholipid, and 10% protein by wt., found predominantly in pulmonary alveoli of vertebrate lungs. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), are present within the alveoli at very high concns., and exert anti-inflammatory effects by regulating multiple Toll like receptors (TLR2/1, TLR4, and TLR2/6) by antagonizing cognate ligand-dependent activation. POPG also attenuates LPS-induced lung injury in vivo. In addn., these lipids bind directly to RSV and influenza A viruses (IAVs) and block interaction between host cells and virions, and thereby prevent viral replication in vitro. POPG and PI also inhibit RSV and IAV infection in vivo, in mice and ferrets. The lipids markedly inhibit SARS-CoV-2 infection in vitro. These findings suggest that both POPG and PI have strong potential to be applied as both prophylaxis and post-infection treatments for problematic respiratory viral infections.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XmtlOjt74%253D&md5=ff9d30f786bd7aef151dcfda693ec9a6
50. 50

    Filion, M. C.; Phillips, N. C. Anti-Inflammatory Activity of Cationic Lipids. Br. J. Pharmacol. 1997, 122 (3), 551– 557,  DOI: 10.1038/sj.bjp.0701396

    Google Scholar

    50

    Anti-inflammatory activity of cationic lipids

    Filion, Mario C.; Phillips, Nigel C.

    British Journal of Pharmacology (1997), 122 (3), 551-557CODEN: BJPCBM; ISSN:0007-1188. (Stockton)

    The effect of liposome phospholipid compn. has been assumed to be relatively unimportant because of the presumed inert nature of phospholipids. We have previously shown that cationic liposome formulations used for gene therapy inhibit, through their cationic component, the synthesis by activated macrophages of the pro-inflammatory mediators nitric oxide (NO) and tumor necrosis factor-α (TNF-α). In this study, we have evaluated the ability of different cationic lipids to reduce footpad inflammation induced by carrageenan and by sheep red blood cell challenge. Parenteral (i.p. or s.c) or local injection of the pos. charged lipids dimethyldioctadecylammomium bromide (DDAB), dioleyoltrimethylammonium propane (DOTAP), dimyristoyltrimethylammonium propane (DMTAP) or dimethylaminoethanecarbamoyl cholesterol (DC-Chol) significantly reduced the inflammation obsd. in both models in a dose-dependent manner (max. inhibition: 70-95%). Cationic lipids assocd. with dioleyol- or dipalmitoyl-phosphatidylethanolamine retained their anti-inflammatory activity while cationic lipids assocd. with dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylglycerol (DMPG) showed no anti-inflammatory activity, indicating that the release of cationic lipids into the macrophage cytoplasm is a necessary step for anti-inflammatory activity. The anti-inflammatory activity of cationic lipids was abrogated by the addn. of dipalmitoylphosphatidylethanolamine-poly(ethylene)glycol-2000 (DPPE-PEG2000) which blocks the interaction of cationic lipids with macrophages. Because of the significant role of protein kinase C (PKC) in the inflammatory process we have detd. whether the cationic lipids used in this study inhibit PKC activity. The cationic lipids significantly inhibited the activity of PKC but not the activity of a non-related protein kinase, PKA. The synthesis of interleukin-6 (IL-6), which is not dependent on PKC activity for its induction in macrophages, was not modified in vitro or in situ by cationic lipids. The synthesis of NO and TNF-α in macrophages, both of which are PKC-dependent, was downregulated by cationic lipids. These results demonstrate that cationic lipids can be considered as novel anti-inflammatory agents. The downregulation of pro-inflammatory mediators through interaction of cationic lipids with the PKC pathway may explain this anti-inflammatory activity. Furthermore, since cationic lipids have intrinsic anti-inflammatory activity, cationic liposomes should be used with caution to deliver nucleic acids for gene therapy in vivo.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXmslChsro%253D&md5=f3c06f2c6c337996e62dc126a74b253e
51. 51

    Kann, O.; Kovács, R. Mitochondria and Neuronal Activity. Am. J. Physiol. Cell Physiol. 2007, 292 (2), C641– C657,  DOI: 10.1152/ajpcell.00222.2006

    Google Scholar

    There is no corresponding record for this reference.
52. 52

    Azzazy, H. M. E.; Hong, K.; Wu, M.-C.; Gross, G. W. Interaction of Cationic Liposomes with Cells of Electrically Active Neuronal Networks in Culture. Brain Res. 1995, 695 (2), 231– 236,  DOI: 10.1016/0006-8993(95)00710-8

    Google Scholar

    52

    Interaction of cationic liposomes with cells of electrically active neuronal networks in culture

    Azzazy, Hassan M. E.; Hong, Keelung; Wu, Ming-Chi; Gross, Guenter W.

    Brain Research (1995), 695 (2), 231-6CODEN: BRREAP; ISSN:0006-8993. (Elsevier)

    Incubation of rhodamine-labeled cationic liposomes with mature murine spinal cultures results in strong fluorescence that is evenly distributed on somata and neurites of neurons in 7 different cultures. Staining of the glial carpet is minimal. Rhodamine-labeled dextran, encapsulated in liposomes, also stains neurons. Electron microscope data show external attachment and intact internalization of liposomes. Spontaneous elec. bursting activity is altered but not lost after incubation.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXos1GgsLY%253D&md5=348198a5383e0a6b25c746051c02e8a8
53. 53

    Cui, S.; Wang, Y.; Gong, Y.; Lin, X.; Zhao, Y.; Zhi, D.; Zhou, Q.; Zhang, S. Correlation of the Cytotoxic Effects of Cationic Lipids with Their Headgroups. Toxicol. Res. 2018, 7 (3), 473– 479,  DOI: 10.1039/C8TX00005K

    Google Scholar

    53

    Correlation of the cytotoxic effects of cationic lipids with their headgroups

    Cui, Shaohui; Wang, Yueying; Gong, Yan; Lin, Xiao; Zhao, Yinan; Zhi, Defu; Zhou, Quan; Zhang, Shubiao

    Toxicology Research (Cambridge, United Kingdom) (2018), 7 (3), 473-479CODEN: TROEE8; ISSN:2045-4538. (Royal Society of Chemistry)

    As effective non-viral vectors of gene therapy, cationic lipids still have the problem of toxicity, which has become one of the main bottlenecks for their applications. The toxicity of cationic lipids is strongly connected to the headgroup structures. In this article, we studied the cytotoxicity of two cationic lipids with a quaternary ammonium headgroup (CDA14) and a tri-peptide headgroup (CDO14), resp., and with the same linker bond and hydrophobic domain. The IC50 values of CDA14 and CDO14 against NCI-H460 cells were 109.4μg mL-1 and 340.5μg mL-1, resp. To det. the effects of headgroup structures of cationic lipids on cytotoxicity, apoptosis related pathways were investigated. As the lipids with a quaternary ammonium headgroup could induce more apoptotic cells than the ones with a peptide headgroup, the enzymic activity of caspase-9 and caspase-3 increased obviously, whereas the mitochondrial membrane potential (MMP) decreased. At the same time, the reactive oxygen species (ROS) levels also increased and the cell cycle was arrested at the S phase. The results showed that the toxicity of the cationic lipid had a close relationship with its headgroup structures, and the cytotoxic mechanism was mainly via the caspase activation dependent signaling pathway and mitochondrial dysfunction. Through this study, we hope to provide the scientific basis for exploiting safer and more efficient cationic lipids for gene delivery.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXltlSrsbk%253D&md5=b8b23f57d8ffba7f960583ad076b394c
54. 54

    Filion, M. C.; Phillips, N. C. Toxicity and Immunomodulatory Activity of Liposomal Vectors Formulated with Cationic Lipids toward Immune Effector Cells. Biochim. Biophys. Acta 1997, 1329 (2), 345– 356,  DOI: 10.1016/S0005-2736(97)00126-0

    Google Scholar

    54

    Toxicity and immunomodulatory activity of liposomal vectors formulated with cationic lipids toward immune effector cells

    Filion, Mario C.; Phillips, Nigel C.

    Biochimica et Biophysica Acta, Biomembranes (1997), 1329 (2), 345-356CODEN: BBBMBS; ISSN:0005-2736. (Elsevier B.V.)

    Liposomal vectors formulated with cationic lipids (cationic liposomes) and fusogenic dioleoylphosphatidylethanolamine (DOPE) have potential for modulating the immune system by delivering gene or antisense oligonucleotide inside immune cells. The toxicity and the immunoadjuvant activity of cationic liposomes contg. nucleic acids toward immune effector cells has not been investigated in detail. In this report, we have evaluated the toxicity of liposomes formulated with various cationic lipids towards murine macrophages and T lymphocytes and the human monocyte-like U937 cell line. The effect of these cationic liposomes on the synthesis of two immunomodulators produced by activated macrophages, nitric oxide (NO) and tumor necrosis factor-α (TNF-α), has also been detd. We have found that liposomes formulated from DOPE and cationic lipids based on diacyltrimethylammonium propane (dioleoyl-, dimyristoyl-, dipalmitoyl-, disteroyl-: DOTAP, DMTAP, DPTAP, DSTAP) or dimethyldioctadecylammonium bromide (DDAB) are highly toxic in vitro toward phagocytic cells (macrophages and U937 cells), but not towards non-phagocytic T lymphocytes. The rank order of toxicity was DOPE/DDAB>DOPE/DOTAP>DOPE/DMTAP>DOPE/DPTAP>DOPE/DSTAP. The ED50's for macrophage toxicity were <10 nmol/mL for DOPE/DDAB, 12 nmol/mL for DOPE/DOTAP, 50 nmol/mL for DOPE/DMTAP, 400 nmol/mL for DOPE/DPTAP and >1000 nmol/mL for DOPE/DSTAP. The incorporation of DNA (antisense oligonucleotide or plasmid vector) into the cationic liposomes marginally reduced their toxicity towards macrophages. Although toxicity was obsd. with cationic lipids alone, it was clearly enhanced by the presence of DOPE. The replacement of DOPE by dipalmitoylphosphatidylcholine (DPPC) significantly reduced liposome toxicity towards macrophages, and the presence of dipalmitoylphosphatidylethanolamine-PEG2000 (DPPE-PEG2000: 10 mol%) in the liposomes completely abolished this toxicity. Cationic liposomes, irresp. of their DNA content, down-regulated NO and TNF-α synthesis by lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-activated macrophages. The replacement of DOPE by DPPC, or the addn. of DPPE-PEG2000, restored NO and TNF-α synthesis by activated macrophages. Since macrophages constitute the major site of liposome localization after parenteral administration and play an important role in the control of the immune system, cationic liposomes should be used with caution to deliver gene or antisense oligonucleotide to mammalian cells. Cationic lipids show in vitro toxicity toward phagocytic cells and inhibit in vitro and in situ NO and TNF-α prodn. by activated macrophages.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXmtVWhtro%253D&md5=67c5042be41cefa20ccdf9b38c97eb55
55. 55

    Takano, S.; Aramaki, Y.; Tsuchiya, S. Physicochemical Properties of Liposomes Affecting Apoptosis Induced by Cationic Liposomes in Macrophages. Pharm. Res. 2003, 20 (7), 962– 968,  DOI: 10.1023/A:1024441702398

    Google Scholar

    55

    Physicochemical Properties of Liposomes Affecting Apoptosis Induced by Cationic Liposomes in Macrophages

    Takano, Shuhei; Aramaki, Yukihiko; Tsuchiya, Seishi

    Pharmaceutical Research (2003), 20 (7), 962-968CODEN: PHREEB; ISSN:0724-8741. (Kluwer Academic/Plenum Publishers)

    Cationic liposomes are expected to be useful as nonviral vectors for gene delivery. Cationic liposomes showed cytotoxicity, and the authors proposed that the cytotoxicity is through apoptosis. In this study, the authors examd. the effects of liposomal properties, such as liposomal charge, size, membrane fluidity, and PEG coating, on the induction of apoptosis in the macrophage-like cell line RAW264.7. RAW264.7 cells were treated with liposomes, and the induction of apoptosis was evaluated by monitoring the changes in DNA content by flow cytometry. The assocn. of liposomes with cells and the generation of reactive oxygen species (ROS) were also measured by flow cytometry. The induction of apoptosis of RAW264.7 cells was dependent on the concns. of stearylamine or cholesterol, a component of cationic liposomes. A significant correlation was obsd. between the degree of apoptosis and assocn. of cationic liposomes with the cells. Coating the liposomal surface with polyethylene glycol (PEG) decreased the assocn. of cationic liposomes with RAW264.7 cells and reduced the induction of apoptosis. Liposomal size also affected the induction of apoptosis, and larger liposomes showed a higher degree of apoptosis induction. Furthermore, ROS, which were required for the induction of apoptosis by cationic liposomes, were generated in a cholesterol content-dependent manner, and ROS generation was also decreased by PEG coating as the assocn. and the induction of apoptosis were reduced. The degree of apoptosis is related to the extent of assocn. of cationic liposomes with cells and is related to the generation of ROS.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXkvFSlurg%253D&md5=7885e7dba11585c3b1324f366d528f52
56. 56

    Arias, J. L. Liposomes in Drug Delivery: A Patent Review (2007 – Present). Expert Opin. Ther. Pat. 2013, 23 (11), 1399– 1414,  DOI: 10.1517/13543776.2013.828035

    Google Scholar

    56

    Liposomes in drug delivery: a patent review (2007 - present)

    Arias, Jose L.

    Expert Opinion on Therapeutic Patents (2013), 23 (11), 1399-1414CODEN: EOTPEG; ISSN:1354-3776. (Informa Healthcare)

    A review. Introduction: Drug therapy is frequently limited by the widespread biodistribution of the active agents and the little specificity for non-healthy cells. Therefore, inadequate drug concns. result into the site of action, and severe toxicity may also arise. To address the problem, liposome-based medicines have tried to improve pharmacotherapy. Areas covered: The review provides an updated revision of the lately published patents covering recent advances in liposome-based drug delivery. They are principally related to the control of drug biodistribution by using stealth, stimuli-sensitive and/or liposomal structures surface modified for ligand-mediated delivery. The contribution further highlights liposome-based theranosis. Expert opinion: Liposomes have received great attention given their biocompatibility, biodegradability and targetability. From 2007 to present date, patent publications related to their use in drug delivery have shown the move towards more stable structures with optimized drug delivery capabilities, further combining passive and active targeting concepts to gain control of the in vivo fate. However, the introduction of all these liposomal structures in the disease arena is still a challenge. Two key aspects are the difficulty of identifying easy and economic synthesis conditions which can be scaled up in the pharmaceutical industry, and the need for complementary investigations illustrating risks of toxicity/immunogenicity.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvVart7zN&md5=11194f00fa0b2bc7b4c823fb8b0b7902
57. 57

    Huang, M.; Liang, C.; Tan, C.; Huang, S.; Ying, R.; Wang, Y.; Wang, Z.; Zhang, Y. Liposome Co-Encapsulation as a Strategy for the Delivery of Curcumin and Resveratrol. Food Funct. 2019, 10 (10), 6447– 6458,  DOI: 10.1039/C9FO01338E

    Google Scholar

    57

    Liposome co-encapsulation as a strategy for the delivery of curcumin and resveratrol

    Huang, Meigui; Liang, Cuiping; Tan, Chen; Huang, Shuai; Ying, Ruifeng; Wang, Yaosong; Wang, Zhenjiong; Zhang, Yifan

    Food & Function (2019), 10 (10), 6447-6458CODEN: FFOUAI; ISSN:2042-6496. (Royal Society of Chemistry)

    Curcumin and resveratrol are natural compds. whose strong antioxidant activities are highly beneficial in the human diet. Unfortunately, their physicochem. properties result in poor stability in their chem. and antioxidant activities, which limits their utilization in food and pharmaceutical applications. In this study, liposomal nanoencapsulation was developed as a strategy to overcome these limitations and improve the antioxidant effects of these compds. The physicochem. characteristics of co-encapsulated liposomes were evaluated and compared to formulations contg. each compd. individually. Liposomes co-encapsulating curcumin and resveratrol presented a lower particle size, lower polydispersity index and greater encapsulation efficiency. The formulation of liposomes co-loading curcumin and resveratrol at 5 : 1, exhibited the lowest particle size (77.50 nm), lowest polydispersity index (0.193), highest encapsulation efficiency (reaching 80.42 ±2.12%), and strongest 2,2-diphenyl-1-picrylhydrazyl scavenging, lipid peroxidn. inhibition capacity and reducing power. Addnl., liposomes loading both curcumin and resveratrol displayed a higher ability during prepn., storage, heating and surfactant shock than those loaded with individual polyphenol. IR spectroscopic and fluorescence techniques demonstrated that the curcumin mainly located in the hydrophobic acyl-chain region of liposomes, while the resveratrol orientated to the polar head groups. These orientations could have synergistic effects on the stabilization of liposomes. Our findings should guide the rational design of a co-delivery liposomal system regarding the location and orientation of bioactive compds. inside the lipid bilayer.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhslaqsbvO&md5=c277156f6d11e647eb9c57d77f561b30
58. 58

    Narayanan, N. K.; Nargi, D.; Randolph, C.; Narayanan, B. A. Liposome Encapsulation of Curcumin and Resveratrol in Combination Reduces Prostate Cancer Incidence in PTEN Knockout Mice. Int. J. Cancer 2009, 125 (1), 1– 8,  DOI: 10.1002/ijc.24336

    Google Scholar

    58

    Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice

    Narayanan, Narayanan K.; Nargi, Dominick; Randolph, Carla; Narayanan, Bhagavathi A.

    International Journal of Cancer (2009), 125 (1), 1-8CODEN: IJCNAW; ISSN:0020-7136. (Wiley-Liss, Inc.)

    Increasing interest in the use of phytochems. to reduce prostate cancer led us to investigate 2 potential agents, curcumin and resveratrol as preventive agents. However, there is concern about the bioavailability of these agents pertinent to the poor absorption and thereby limiting its clin. use. With the view to improve their bioavailability, we used the liposome encapsulated curcumin, and resveratrol individually and in combination in male B6C3F1/J mice. Further, we examd. the chemopreventive effect of liposome encapsulated curcumin and resveratrol in combination in prostate-specific PTEN knockout mice. In vitro assays using PTEN-CaP8 cancer cells were performed to investigate the combined effects curcumin with resveratrol on (i) cell growth, apoptosis and cell cycle (ii) impact on activated p-Akt, cyclin D1, m-TOR and androgen receptor (AR) proteins involved in tumor progression. HPLC anal. of serum and prostate tissues showed a significant increase in curcumin level when liposome encapsulated curcumin coadministered with liposomal resveratrol (p < 0.001). Combination of liposomal forms of curcumin and resveratrol significantly decreased prostatic adenocarcinoma in vivo (p < 0.001). In vitro studies revealed that curcumin plus resveratrol effectively inhibit cell growth and induced apoptosis. Mol. targets activated due to the loss of phosphatase and tensin homolog (PTEN) including p-Akt, cyclin D1, mammalian target of rapamycin and AR were downregulated by these agents in combination. Findings from this study for the first time provide evidence on phytochems. in combination to enhance chemopreventive efficacy in prostate cancer. These findings clearly suggest that phytochems. in combination may reduce prostate cancer incidence due to the loss of the tumor suppressor gene PTEN. © 2009 UICC.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXmslCguro%253D&md5=2ccc967645875f5fefabd74bd6315f6c
59. 59

    Soo, E.; Thakur, S.; Qu, Z.; Jambhrunkar, S.; Parekh, H. S.; Popat, A. Enhancing Delivery and Cytotoxicity of Resveratrol through a Dual Nanoencapsulation Approach. J. Colloid Interface Sci. 2016, 462, 368– 374,  DOI: 10.1016/j.jcis.2015.10.022

    Google Scholar

    59

    Enhancing delivery and cytotoxicity of resveratrol through a dual nanoencapsulation approach

    Soo, Ernest; Thakur, Sachin; Qu, Zhi; Jambhrunkar, Siddharth; Parekh, Harendra S.; Popat, Amirali

    Journal of Colloid and Interface Science (2016), 462 (), 368-374CODEN: JCISA5; ISSN:0021-9797. (Elsevier B.V.)

    Despite the known anticancer potential of resveratrol, its clin. applications are often hindered by physicochem. limitations such as poor soly. and stability. The encapsulation of resveratrol in formulations such as polymeric nanoparticles and liposomes has shown limited success. This study aimed to develop and optimize a novel drug carrier by co-encapsulating pristine resveratrol alongside cyclodextrin-resveratrol inclusion complexes in the lipophilic and hydrophilic compartments of liposomes, resp. by using a novel dual carrier approach. The particle size, polydispersity index and zeta potential of the final formulation were 131 ± 1.30 nm, 0.089 ± 0.005 and -2.64 ± 0.51 mV, resp. Compared to free resveratrol and conventional liposomal formulations with drug release profile of 40-60%, our novel nanoformulations showed complete (100%) drug release in 24 h. The formulation was stable for 14 days at 4 °C. We also studied the in vitro cytotoxicity of resveratrol encapsulated liposomes in HT-29 colon cancer cell lines. The cytotoxicity profile of our liposomes was obsd. to be dose dependent and enhanced in comparison to free resveratrol (in DMSO). Our study demonstrates that co-encapsulation of pristine resveratrol along with its cyclodextrin complex in liposomal formulations is a plausible option for the enhanced delivery of the hydrophobic chemotherapeutic agent.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslGmurjL&md5=b1ad82a1c6ef4c68f0ef39574a4d787d
60. 60

    Wei, X.-Q.; Zhu, J.-F.; Wang, X.-B.; Ba, K. Improving the Stability of Liposomal Curcumin by Adjusting the Inner Aqueous Chamber pH of Liposomes. ACS Omega 2020, 5 (2), 1120– 1126,  DOI: 10.1021/acsomega.9b03293

    Google Scholar

    60

    Improving the Stability of Liposomal Curcumin by Adjusting the Inner Aqueous Chamber pH of Liposomes

    Wei, Xue-Qin; Zhu, Juan-Fang; Wang, Xin-Bo; Ba, Kai

    ACS Omega (2020), 5 (2), 1120-1126CODEN: ACSODF; ISSN:2470-1343. (American Chemical Society)

    Curcumin (CURC) is a hydrophobic mol. and its water soly. can be greatly improved by liposome encapsulation. However, investigations on the stability of pH-sensitive mols. incorporated into liposomal membranes are limited. In this study, CURC-loaded liposomes with varied internal pH values (pH 2.5, 5.0, or 7.4) were prepd. and designated as CURC-LP (pH 2.5), CURC-LP (pH 5.0), and CURC-LP (pH 7.4). Phys. properties including particle size, ζ-potential, morphol., entrapment efficiency, and phys. stabilities of these CURC-LPs were assessed. In addn., the chem. stability of liposomal CURC to different external physiol. environments and internal microenvironmental pH levels were investigated. We found that among these CURC-LPs, CURU-LP (pH 2.5) has the highest entrapment efficiency (73.7%), the best phys. stabilities, and the slowest release rate in vitro. Liposomal CURC remains more stable in an acid external environment. In the physiol. environment, the chem. stability of liposomal CURC is microenvironmental pH-dependent. In conclusion, we prove that the stability of liposomal CURC is external physiol. environment- and internal microenvironmental pH-dependent. These findings suggest that creating an acidic microenvironment in the internal chamber of liposomes is beneficial to the stability of liposomal CURC, as well as for other pH-sensitive mols.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXksVyhtQ%253D%253D&md5=0a183cdf21bcf350f2c1d10fb743e96d
61. 61

    Peng, R.-M.; Lin, G.-R.; Ting, Y.; Hu, J.-Y. Oral Delivery System Enhanced the Bioavailability of Stilbenes: Resveratrol and Pterostilbene. Biofactors 2018, 44 (1), 5– 15,  DOI: 10.1002/biof.1405

    Google Scholar

    61

    Oral delivery system enhanced the bioavailability of stilbenes: resveratrol and pterostilbene

    Peng, Ru-Min; Lin, Guan-Ru; Ting, Yuwen; Hu, Jing-Yu

    BioFactors (2018), 44 (1), 5-15CODEN: BIFAEU; ISSN:1872-8081. (Wiley-Blackwell)

    A review. Stilbenes are a large group of compds. with the C6-C2-C6 skeleton, in which two arom. rings are connected by an ethylene bridge. Resveratrol and its structural analog, pterostilbene, are by far the two most widely researched stilbenes in terms of their beneficial bioactivities. However, the bioefficacy of these compds. is greatly reduced when consumed orally due to their poor aq. soly., which leads to poor bioavailability. To overcome the limitation, strategies improving their soly., absorption, and systemic concn. were applied when designing a suitable edible delivery system. This review will summarize the findings from the studies evaluating the oral bioavailability of stilbenes with emphasize on the resveratrol and pterostilbene. It will also include the edible delivery systems currently available and their effect on the oral bioavailability. 2018 BioFactors, 2018.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmtlWqug%253D%253D&md5=e08c0d33e246e88df70079faef9a80fb
62. 62

    Nasri, H.; Baradaran, A.; Shirzad, H.; Rafieian-Kopaei, M. New Concepts in Nutraceuticals as Alternative for Pharmaceuticals. Int. J. Prev. Med. 2014, 5 (12), 1487– 1499

    Google Scholar

    62

    New concepts in nutraceuticals as alternative for pharmaceuticals

    Nasri Hamid; Baradaran Azar; Shirzad Hedayatollah; Rafieian-Kopaei Mahmoud

    International journal of preventive medicine (2014), 5 (12), 1487-99 ISSN:2008-7802.

    Nutraceuticals are products, which other than nutrition are also used as medicine. A nutraceutical product may be defined as a substance, which has physiological benefit or provides protection against chronic disease. Nutraceuticals may be used to improve health, delay the aging process, prevent chronic diseases, increase life expectancy, or support the structure or function of the body. Nowadays, nutraceuticals have received considerable interest due to potential nutritional, safety and therapeutic effects. Recent studies have shown promising results for these compounds in various complications. In the present review much effort has been devoted to present new concepts about nutraceuticals based on their diseases modifying indications. Emphasis has been made to present herbal nutraceuticals effective on hard curative disorders related to oxidative stress including allergy, alzheimer, cardiovascular, cancer, diabetes, eye, immune, inflammatory and Parkinson's diseases as well as obesity. The recently published papers about different aspects of nutraceuticals as alternative for pharmaceuticals were searched using scientific sites such as Medline, PubMed, and Google Scholar. The used terms included nutraceutical and allergy, alzheimer, cardiovascular, cancer, diabetes, eye, immune, inflammatory or Parkinson.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2Mrotlaktg%253D%253D&md5=b0307491485738ea3431622b8df53962
63. 63

    Tauskela, J. S.; Aylsworth, A.; Hewitt, M.; Brunette, E.; Blondeau, N. Failure and Rescue of Preconditioning-Induced Neuroprotection in Severe Stroke-like Insults. Neuropharmacology 2016, 105, 533– 542,  DOI: 10.1016/j.neuropharm.2016.02.007

    Google Scholar

    63

    Failure and rescue of preconditioning-induced neuroprotection in severe stroke-like insults

    Tauskela, Joseph S.; Aylsworth, Amy; Hewitt, Melissa; Brunette, Eric; Blondeau, Nicolas

    Neuropharmacology (2016), 105 (), 533-542CODEN: NEPHBW; ISSN:0028-3908. (Elsevier B.V.)

    Preconditioning is a well established neuroprotective modality. However, the mechanism and relative efficacy of neuroprotection between diverse preconditioners is poorly defined. Cultured neurons were preconditioned by 4-aminopyridine and bicuculline (4-AP/bic), rendering neurons tolerant to normally lethal (sufficient to kill most neurons) oxygen-glucose deprivation (OGD) or a chem. OGD-mimic, ouabain/TBOA, by suppression of extracellular glutamate (glutamate ex) elevations. However, subjecting preconditioned neurons to longer-duration supra-lethal insults caused neurotoxic glutamate ex elevations, thereby identifying a 'ceiling' to neuroprotection. Neuroprotective 'rescue' of neurons could be obtained by administration of an NMDA receptor antagonist, MK-801, just before glutamate ex rose during these supra-lethal insults. Next, we evaluated if these concepts of glutamate ex suppression during lethal OGD, and a neuroprotective ceiling requiring MK-801 rescue under supra-lethal OGD, extended to the preconditioning field. In screening a panel of 42 diverse putative preconditioners, neuroprotection against normally lethal OGD was obsd. in 12 cases, which correlated with glutamate ex suppression, both of which could be reversed, either by the inclusion of a glutamate uptake inhibitor (TBOA, to increase glutamate ex levels) during OGD or by exposure to supra-lethal OGD. Administrating MK-801 during the latter stages of supra-lethal OGD again rescued neurons, although to varying degrees dependent on the preconditioning agent. Thus, 'stress-testing' against the harshest ischemic-like insults yet tested identifies the most efficacious preconditioners, which dictates how early MK-801 needs to be administered during the insult in order to maintain neuroprotection. Preconditioning delays a neurotoxic rise in glutamate ex levels, thereby 'buying time' for acute anti-excitotoxic pharmacol. rescue.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XjsFeqsrk%253D&md5=145ebed582705da1359c4ed69e64a3a8
64. 64

    Vohlídalová, E. Inkorporace Macasiamenene F Do Liposomů – Fyzikální Charakterizace [Incorporation of Macasiamenene F into Liposomes – Physical Characterization, Advanced Master’s Thesis; Veterinární a Farmaceutická Univerzita Brno: Brno, 2020.

    Google Scholar

    There is no corresponding record for this reference.
65. 65

    Blasi, E.; Barluzzi, R.; Bocchini, V.; Mazzolla, R.; Bistoni, F. Immortalization of Murine Microglial Cells by a V-Raf/v-Myc Carrying Retrovirus. J. Neuroimmunol. 1990, 27 (2–3), 229– 237,  DOI: 10.1016/0165-5728(90)90073-V

    Google Scholar

    65

    Immortalization of murine microglial cells by a v-raf/v-myc carrying retrovirus

    Blasi E; Barluzzi R; Bocchini V; Mazzolla R; Bistoni F

    Journal of neuroimmunology (1990), 27 (2-3), 229-37 ISSN:0165-5728.

    A murine cell line (BV-2) has been generated by infecting primary microglial cell cultures with a v-raf/v-myc oncogene carrying retrovirus (J2). BV-2 cells expressed nonspecific esterase activity, phagocytic ability and lacked peroxidase activity. Such cells secreted lysozyme and, following appropriate stimulation, also interleukin 1 and tumor necrosis factor. Furthermore, BV-2 cells exhibited spontaneous anti-Candida activity and acquired tumoricidal activity upon treatment with interferon-gamma. Phenotypically, BV-2 cells resulted positive for MAC1 and MAC2 antigens, and negative for MAC3, glial fibrillary acidic protein (GFAP) and galactocerebroside (GC) antigens. Since BV-2 cells retain most of the morphological, phenotypical and functional properties described for freshly isolated microglial cells, we can conclude that J2 virus infection has resulted in the immortalization of active microglial cells.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK3c3jslWruw%253D%253D&md5=0c9d936da27e08fc8e21b4d269405618
66. 66

    Bourourou, M.; Gouix, E.; Melis, N.; Friard, J.; Heurteaux, C.; Tauc, M.; Blondeau, N. Inhibition of eIF5A Hypusination Pathway as a New Pharmacological Target for Stroke Therapy. J. Cereb. Blood Flow Metab. 2021, 41 (5), 1080– 1090,  DOI: 10.1177/0271678X20928882

    Google Scholar

    66

    Inhibition of eIF5A hypusination pathway as a new pharmacological target for stroke therapy

    Bourourou, Miled; Gouix, Elsa; Melis, Nicolas; Friard, Jonas; Heurteaux, Catherine; Tauc, Michel; Blondeau, Nicolas

    Journal of Cerebral Blood Flow & Metabolism (2021), 41 (5), 1080-1090CODEN: JCBMDN; ISSN:0271-678X. (Sage Publications)

    In eukaryotes, the polyamine pathway generates spermidine that activates the hypusination of the translation factor eukaryotic initiation factor 5A (eIF5A). Evidence in model organisms like drosophila suggests that targeting polyamines synthesis might be of interest against ischemia. However, the potential of targeting eIF5A hypusination in stroke, the major therapeutic challenge specific to ischemia, is currently unknown. Using in vitro models of ischemic-related stress, we documented that GC7, a specific inhibitor of a key enzyme in the eIF5A activation pathway, affords neuronal protection. We identified the preservation of mitochondrial function and thereby the prevention of toxic ROS generation as major processes of GC7 protection. To represent a thoughtful opportunity of clin. translation, we explored whether GC7 administration reduces the infarct vol. and functional deficits in an in vivo transient focal cerebral ischemia (tFCI) model in mice. A single GC7 pre- or post-treatment significantly reduces the infarct vol. post-stroke. Moreover, GC7-post-treatment significantly improves mouse performance in the rotarod and Morris water-maze, highlighting beneficial effects on motor and cognitive post-stroke deficits. Our results identify the targeting of the polyamine-eIF5A-hypusine axis as a new therapeutic opportunity and new paradigm of research in stroke and ischemic diseases.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXptFWjt74%253D&md5=674a0bbf2c493ff64f505066bec77474
67. 67

    Triantafilou, K.; Triantafilou, M.; Dedrick, R. L. A CD14-Independent LPS Receptor Cluster. Nat. Immunol. 2001, 2 (4), 338,  DOI: 10.1038/86342

    Google Scholar

    67

    A CD14-independent LPS receptor cluster

    Triantafilou, Kathy; Triantafilou, Martha; Dedrick, Russell L.

    Nature Immunology (2001), 2 (4), 338-345CODEN: NIAMCZ; ISSN:1529-2908. (Nature America Inc.)

    Bacterial lipopolysaccharide (LPS), the major structural component of the outer wall of Gram-neg. bacteria, is a potent initiator of an inflammatory response and serves as an indicator of bacterial infection. Although CD14 has been identified as the main LPS receptor, accumulating evidence has suggested the possible existence of other functional receptor(s). Here, using affinity chromatog., peptide mass fingerprinting, and fluorescence resonance energy transfer, the authors have identified 4 new proteins that form an activation cluster after LPS ligation and are involved in LPS signal transduction. The authors present evidence that implicates heat shock proteins 70 and 90, chemokine receptor 4, and growth differentiation factor 5 as the main mediators of activation by bacterial lipopolysaccharide.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXis1aktb8%253D&md5=3c06e8ebf1afc2b9c06a628324a316ca
68. 68

    Taka, E.; Mazzio, E. A.; Goodman, C. B.; Redmon, N.; Flores-Rozas, H.; Reams, R.; Darling-Reed, S.; Soliman, K. F. A. Anti-Inflammatory Effects of Thymoquinone in Activated BV-2 Microglia Cells. J. Neuroimmunol. 2015, 286, 5– 12,  DOI: 10.1016/j.jneuroim.2015.06.011

    Google Scholar

    68

    Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells

    Taka, Equar; Mazzio, Elizabeth A.; Goodman, Carl B.; Redmon, Natalie; Flores-Rozas, Hernan; Reams, Renee; Darling-Reed, Selina; Soliman, Karam F. A.

    Journal of Neuroimmunology (2015), 286 (), 5-12CODEN: JNRIDW; ISSN:0165-5728. (Elsevier B.V.)

    Thymoquinone (TQ), the main pharmacol. active ingredient within the black cumin seed (Nigella sativa) is believed to be responsible for the therapeutic effects on chronic inflammatory conditions such as arthritis, asthma and neurodegeneration. In this study, we evaluated the potential anti-inflammatory role of TQ in lipopolysaccharide (LPS)-stimulated BV-2 murine microglia cells. The results obtained indicate that TQ was effective in reducing NO2- with an IC50 of 5.04 μM, relative to selective iNOS inhibitor LNIL-L-N6-(1-iminoethyl)lysine (IC50 4.09 μM). TQ mediated redn. in NO2- was found to parallel the decline of iNOS protein expression as confirmed by immunocytochem. In addn., we evaluated the anti-inflammatory effects of TQ on ninety-six (96) cytokines using a RayBio AAM-CYT-3 and 4 cytokine antibody protein array. Data obtained establish a baseline protein expression profile characteristic of resting BV-2 cells in the order of osteopontin > MIP-1alpha > MIP-1 g > IGF-1 and MCP-I. In the presence of LPS [1 ug/mL], activated BV-2 cells produced a sharp rise in specific pro-inflammatory cytokines/chemokine's IL-6, IL-12p40/70, CCL12 /MCP-5, CCL2/MCP-1, and G-CSF which were attenuated by the addn. of TQ (10 μM). The TQ mediated attenuation of MCP-5, MCP-1 and IL-6 protein in supernatants from activated BV-2 cells were corroborated by independent ELISA. Moreover, the data obtained from the RT2 PCR demonstrated a similar pattern where the LPS mediated elevation of mRNA for IL-6, CCL12/MCP-5, CCL2/MCP-1 were significantly attenuated by TQ (10 μM). Also, in this study, consistent data were obtained for both protein antibody array densitometry and ELISA assays. In addn., TQ was found to reduce LPS mediated elevation in gene expression of Cxcl10 and a no. of other cytokines in the panel. These findings demonstrate the significant anti-inflammatory properties of TQ in LPS activated microglial cells. Therefore, the obtained results might indicate the usefulness of TQ in delaying the onset of inflammation-mediated neurodegenerative disorders involving activated microglia cells.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtFaitLjK&md5=1f22baab9a3a7170b1835464a9444779