Sirolimus Encapsulated Liposomes for Cancer Therapy: Physicochemical and Mechanical Characterization of Sirolimus Distribution within Liposome Bilayers
- Ichioma Onyesom ,
- Dimitrios A. Lamprou ,
- Lamprini Sygellou ,
- Samuel K. Owusu-Ware ,
- Milan Antonijevic ,
- Babur Z. Chowdhry , and
- Dennis Douroumis
Abstract

Sirolimus has recently been introduced as a therapeutic agent for breast and prostate cancer. In the current study, conventional and Stealth liposomes were used as carriers for the encapsulation of sirolimus. The physicochemical characteristics of the sirolimus liposome nanoparticles were investigated including the particle size, zeta potential, stability and membrane integrity. In addition atomic force microscopy was used to study the morphology, surface roughness and mechanical properties such as elastic modulus deformation and deformation. Sirolimus encapsulation in Stealth liposomes showed a high degree of deformation and lower packing density especially for dipalmitoyl-phosphatidylcholine (DPPC) Stealth liposomes compared to unloaded. Similar results were obtained by differential scanning calorimetry (DSC) studies; sirolimus loaded liposomes were found to result in a distorted state of the bilayer. X-ray photon electron (XPS) analysis revealed a uniform distribution of sirolimus in multilamellar DPPC Stealth liposomes compared to a nonuniform, greater outer layer lamellar distribution in distearoylphosphatidylcholine (DSPC) Stealth liposomes.
Cited By
This article is cited by 23 publications.
- Cristian M. O. Lépori, N. Mariano Correa, Juana J. Silber, R. Darío Falcone, Manuel López-López, M. Luisa Moyá. Use of Ionic Liquids-like Surfactants for the Generation of Unilamellar Vesicles with Potential Applications in Biomedicine. Langmuir 2019, 35 (41) , 13332-13339. https://doi.org/10.1021/acs.langmuir.9b01197
- Ling Chen, Rong Liang, Yihan Wang, Wallace Yokoyama, Maoshen Chen, Fang Zhong. Characterizations on the Stability and Release Properties of β-ionone Loaded Thermosensitive Liposomes (TSLs). Journal of Agricultural and Food Chemistry 2018, 66 (31) , 8336-8345. https://doi.org/10.1021/acs.jafc.7b06130
- Sarthak Mandal, Jagannath Kuchlyan, Surajit Ghosh, Chiranjib Banerjee, Niloy Kundu, Debasis Banik, and Nilmoni Sarkar . Vesicles Formed in Aqueous Mixtures of Cholesterol and Imidazolium Surface Active Ionic Liquid: A Comparison with Common Cationic Surfactant by Water Dynamics. The Journal of Physical Chemistry B 2014, 118 (22) , 5913-5923. https://doi.org/10.1021/jp501033n
- Luciana V. Rebouças, Fátima C.E. Oliveira, Daniel P. Pinheiro, Maria Francilene S. Silva, Vanessa Pinheiro G. Ferreira, Roberto Nicolete, Augusto C.A. Oliveira, Renata G. Almeida, Eufrânio N. da Silva Júnior, Marcia S. Rizzo, Marcília P. Costa, Guilherme Zocolo, Fábio O.S. Ribeiro, Durcilene A. da Silva, Claudia Pessoa. Liposomes containing 3-arylamino-nor-β-lapachone derivative: Development, characterization, and in vitro evaluation of the cytotoxic activity. Journal of Drug Delivery Science and Technology 2021, 62 , 102348. https://doi.org/10.1016/j.jddst.2021.102348
- Uttom Nandi, Ichioma Onyesom, Dennis Douroumis. An in vitro evaluation of antitumor activity of sirolimus-encapsulated liposomes in breast cancer cells. Journal of Pharmacy and Pharmacology 2021, 73 (3) , 300-309. https://doi.org/10.1093/jpp/rgaa061
- Uttom Nandi, Ichioma Onyesom, Dennis Douroumis. Anti-cancer activity of sirolimus loaded liposomes in prostate cancer cell lines. Journal of Drug Delivery Science and Technology 2021, 61 , 102200. https://doi.org/10.1016/j.jddst.2020.102200
- Parijat Kanaujia, Ponnammal Poovizhi, Wai Kiong Ng, Reginald B. H. Tan. Preparation, Characterization and Prevention of Auto-oxidation of Amorphous Sirolimus by Encapsulation in Polymeric Films Using Hot Melt Extrusion. Current Drug Delivery 2019, 16 (7) , 663-671. https://doi.org/10.2174/1567201816666190416123939
- Asmita Das, Pangwan M. Konyak, Argha Das, Subrata Kumar Dey, Chabita Saha. Physicochemical characterization of dual action liposomal formulations: anticancer and antimicrobial. Heliyon 2019, 5 (8) , e02372. https://doi.org/10.1016/j.heliyon.2019.e02372
- Mayara Rodrigues Brandão De Paiva, Nayara Almeida Lage, Maria Carolina Andrade Guerra, Marcos Paulo Gomes Mol, Marcela Coelho Silva Ribeiro, Gustavo De Oliveira Fulgêncio, Dawidson A. Gomes, Isabela Da Costa César, Sílvia Ligório Fialho, Armando Silva-Cunha. Toxicity and in vivo release profile of sirolimus from implants into the vitreous of rabbits’ eyes. Documenta Ophthalmologica 2019, 138 (1) , 3-19. https://doi.org/10.1007/s10633-018-9664-8
- Danina Krajišnik, Jela Milić, Snežana Savić. Challenges of in vitro characterization of nonbiological complex drugs: Example of parenteral preparations with liposomal drug carriers. Arhiv za farmaciju 2019, 69 (4) , 176-198. https://doi.org/10.5937/arhfarm1903176K
- Emiliano Laudadio, Cristina Minnelli, Adolfo Amici, Luca Massaccesi, Giovanna Mobbili, Roberta Galeazzi. Liposomal Formulations for an Efficient Encapsulation of Epigallocatechin-3-Gallate: An In-Silico/Experimental Approach. Molecules 2018, 23 (2) , 441. https://doi.org/10.3390/molecules23020441
- Arpita Roy, Sangita Kundu, Rupam Dutta, Nilmoni Sarkar. Influence of bile salt on vitamin E derived vesicles involving a surface active ionic liquid and conventional cationic micelle. Journal of Colloid and Interface Science 2017, 501 , 202-214. https://doi.org/10.1016/j.jcis.2017.04.051
- Lijuan Pang, Matthew S. Macauley, Britni M. Arlian, Corwin M. Nycholat, James C. Paulson. Encapsulating an Immunosuppressant Enhances Tolerance Induction by Siglec-Engaging Tolerogenic Liposomes. ChemBioChem 2017, 18 (13) , 1226-1233. https://doi.org/10.1002/cbic.201600702
- Qianqian Wang, Tingting Zhao, Yanping Liu, Shanshan Xing, Lei Li, Dawei Gao. An evaluation of anti-tumor effect and toxicity of PEGylated ursolic acid liposomes. Journal of Nanoparticle Research 2016, 18 (2) https://doi.org/10.1007/s11051-016-3339-8
- Christina Karavasili, Nikolaos Bouropoulos, Lamprini Sygellou, Elsa P. Amanatiadou, Ioannis S. Vizirianakis, Dimitrios G. Fatouros. PLGA/DPPC/trimethylchitosan spray-dried microparticles for the nasal delivery of ropinirole hydrochloride: in vitro , ex vivo and cytocompatibility assessment. Materials Science and Engineering: C 2016, 59 , 1053-1062. https://doi.org/10.1016/j.msec.2015.11.028
- Dimitrios A. Lamprou, James R. Smith. Applications of AFM in Pharmaceutical Sciences. 2016,,, 649-674. https://doi.org/10.1007/978-1-4939-4029-5_20
- Mónica Anayántzin Linares-Alba, Magda Berenice Gómez-Guajardo, Joice Furtado Fonzar, Dennis E. Brooks, Gustavo Adolfo García-Sánchez, Maria Josefa Bernad-Bernad. Preformulation Studies of a Liposomal Formulation Containing Sirolimus for the Treatment of Dry Eye Disease. Journal of Ocular Pharmacology and Therapeutics 2016, 32 (1) , 11-22. https://doi.org/10.1089/jop.2015.0032
- Maria-Lucia Briuglia, Chiara Rotella, Amber McFarlane, Dimitrios A. Lamprou. Influence of cholesterol on liposome stability and on in vitro drug release. Drug Delivery and Translational Research 2015, 5 (3) , 231-242. https://doi.org/10.1007/s13346-015-0220-8
- Shuqin Xia, Chen Tan, Yating Zhang, Shabbar Abbas, Biao Feng, Xiaoming Zhang, Fang Qin. Modulating effect of lipid bilayer–carotenoid interactions on the property of liposome encapsulation. Colloids and Surfaces B: Biointerfaces 2015, 128 , 172-180. https://doi.org/10.1016/j.colsurfb.2015.02.004
- Cristian C. Villa, N. Mariano Correa, Juana J. Silber, Fernando Moyano, R. Darío Falcone. Singularities in the physicochemical properties of spontaneous AOT-BHD unilamellar vesicles in comparison with DOPC vesicles. Physical Chemistry Chemical Physics 2015, 17 (26) , 17112-17121. https://doi.org/10.1039/C5CP02387D
- Chen Tan, Yating Zhang, Shabbar Abbas, Biao Feng, Xiaoming Zhang, Shuqin Xia, Dawei Chang. Insights into chitosan multiple functional properties: the role of chitosan conformation in the behavior of liposomal membrane. Food & Function 2015, 6 (12) , 3702-3711. https://doi.org/10.1039/C5FO00256G
- Xiaobo Luo, Rongfa Guan, Xiaoqiang Chen, Miao Tao, Jieqing Ma, Jin Zhao. Optimization on condition of epigallocatechin-3-gallate (EGCG) nanoliposomes by response surface methodology and cellular uptake studies in Caco-2 cells. Nanoscale Research Letters 2014, 9 (1) https://doi.org/10.1186/1556-276X-9-291
- Ayman M. Gebril, Dimitrios A. Lamprou, Manal M. Alsaadi, William H. Stimson, Alexander B. Mullen, Valerie A. Ferro. Assessment of the antigen-specific antibody response induced by mucosal administration of a GnRH conjugate entrapped in lipid nanoparticles. Nanomedicine: Nanotechnology, Biology and Medicine 2014, 10 (5) , e971-e979. https://doi.org/10.1016/j.nano.2013.12.005



