Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect
ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Large-Scale Synthesis of Lipid–Polymer Hybrid Nanoparticles Using a Multi-Inlet Vortex Reactor

View Author Information
† ‡ Department of NanoEngineering, Moores Cancer Center, and §Department of Ophthalmology and Shiley Eye Center, University of California, San Diego, La Jolla, California 92093, United States
Department of Ophthalmology and Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
*Tel.: 858-246-0999. Fax: 858-534-9553. E-mail: [email protected]
Cite this: Langmuir 2012, 28, 39, 13824–13829
Publication Date (Web):September 5, 2012
https://doi.org/10.1021/la303012x
Copyright © 2012 American Chemical Society

    Article Views

    1696

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options

    Abstract

    Abstract Image

    Lipid–polymer hybrid nanoparticles combine the advantages of both polymeric and liposomal drug carriers and have shown great promise as a controlled drug delivery platform. Herein, we demonstrate that it is possible to adapt a multi-inlet vortex reactor (MIVR) for use in the large-scale synthesis of these hybrid nanoparticles. Several parameters, including formulation, polymer concentration, and flow rate, are systematically varied, and the effects of each on nanoparticle properties are studied. Particles fabricated from this process display characteristics that are on par with those made on the lab-scale such as small size, low polydispersity, and excellent stability in both PBS and serum. Using this approach, production rates of greater than 10 g/h can readily be achieved, demonstrating that use of the MIVR is a viable method of producing hybrid nanoparticles in clinically relevant quantities.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    Cited By

    This article is cited by 57 publications.

    1. Prabhat Kattel, Shoukath Sulthana, Jiří Trousil, Dinesh Shrestha, David Pearson, Santosh Aryal. Effect of Nanoparticle Weight on the Cellular Uptake and Drug Delivery Potential of PLGA Nanoparticles. ACS Omega 2023, 8 (30) , 27146-27155. https://doi.org/10.1021/acsomega.3c02273
    2. Joseph Rosenfeld, Francois Ganachaud, Daeyeon Lee. Modulation of Oil/Polymer Nanocapsule Size via Phase Diagram-Guided Microfluidic Coprecipitation. Langmuir 2023, 39 (15) , 5477-5485. https://doi.org/10.1021/acs.langmuir.3c00183
    3. Eshu Middha, Bin Liu. Nanoparticles of Organic Electronic Materials for Biomedical Applications. ACS Nano 2020, 14 (8) , 9228-9242. https://doi.org/10.1021/acsnano.0c02651
    4. Keith Henry Moss, Petya Popova, Sine R. Hadrup, Kira Astakhova, Maria Taskova. Lipid Nanoparticles for Delivery of Therapeutic RNA Oligonucleotides. Molecular Pharmaceutics 2019, 16 (6) , 2265-2277. https://doi.org/10.1021/acs.molpharmaceut.8b01290
    5. Anuja Bokare, Ashley Takami, Jung Han Kim, Alexis Dong, Alan Chen, Ronald Valerio, Steven Gunn, Folarin Erogbogbo. Herringbone-Patterned 3D-Printed Devices as Alternatives to Microfluidics for Reproducible Production of Lipid Polymer Hybrid Nanoparticles. ACS Omega 2019, 4 (3) , 4650-4657. https://doi.org/10.1021/acsomega.9b00128
    6. Philipp Erni and Amal Elabbadi . Free Impinging Jet Microreactors: Controlling Reactive Flows via Surface Tension and Fluid Viscoelasticity. Langmuir 2013, 29 (25) , 7812-7824. https://doi.org/10.1021/la401017z
    7. Saber Imani, Oya Tagit, Chantal Pichon. Neoantigen vaccine nanoformulations based on Chemically synthesized minimal mRNA (CmRNA): small molecules, big impact. npj Vaccines 2024, 9 (1) https://doi.org/10.1038/s41541-024-00807-1
    8. Indhumathi Thirugnanasambandham, Veera Venkata Satyanarayana Reddy Karri, Sukriti Vishwas, Sachin Kumar Singh, Kamal Dua, Gowthamarajan Kuppusamy. Converging paths: Microneedle-based dual intervention of IL-23/IL-17 axis and granuloma formation in rheumatoid nodules. Medical Hypotheses 2024, 189 , 111399. https://doi.org/10.1016/j.mehy.2024.111399
    9. Shama Parveen, Pratishtha Gupta, Saurabh Kumar, Monisha Banerjee. Lipid polymer hybrid nanoparticles as potent vehicles for drug delivery in cancer therapeutics. Medicine in Drug Discovery 2023, 20 , 100165. https://doi.org/10.1016/j.medidd.2023.100165
    10. Mulan Li, Ying Liu, Youhuan Gong, Xiaojie Yan, Le Wang, Wenfu Zheng, Hao Ai, Yuliang Zhao. Recent advances in nanoantibiotics against multidrug-resistant bacteria. Nanoscale Advances 2023, 5 (23) , 6278-6317. https://doi.org/10.1039/D3NA00530E
    11. Huoyue Lin, Jing Leng, Pingqing Fan, Zixing Xu, Gang Ruan. Scalable production of microscopic particles for biological delivery. Materials Advances 2023, 4 (14) , 2885-2908. https://doi.org/10.1039/D3MA00021D
    12. Xing Liang, Mian Wu, Yang Yang, Dandan Liu, Xiaobing Li. Shale gas hydraulic fracturing flowback fluid treatment using a modified vortex flocculation reactor: Effects of the axial and tangential inlet angles. Chemical Engineering Science 2023, 275 , 118713. https://doi.org/10.1016/j.ces.2023.118713
    13. Richa Dave, Rashmin Patel, Mrunali Patel. Hybrid lipid-polymer nanoplatform: A systematic review for targeted colorectal cancer therapy. European Polymer Journal 2023, 186 , 111877. https://doi.org/10.1016/j.eurpolymj.2023.111877
    14. Naveen Rajana, Aare Mounika, Padakanti Sandeep Chary, Valamla Bhavana, Anuradha Urati, Dharmendra Khatri, Shashi Bala Singh, Neelesh Kumar Mehra. Multifunctional hybrid nanoparticles in diagnosis and therapy of breast cancer. Journal of Controlled Release 2022, 352 , 1024-1047. https://doi.org/10.1016/j.jconrel.2022.11.009
    15. Yedi Herdiana, Nasrul Wathoni, Shaharum Shamsuddin, Muchtaridi Muchtaridi. Scale-up polymeric-based nanoparticles drug delivery systems: Development and challenges. OpenNano 2022, 7 , 100048. https://doi.org/10.1016/j.onano.2022.100048
    16. Rania Djermane, Celia Nieto, Julio C. Vargas, Milena Vega, Eva M. Martín del Valle. Insight into the influence of the polymerization time of polydopamine nanoparticles on their size, surface properties and nanomedical applications. Polymer Chemistry 2022, 13 (2) , 235-244. https://doi.org/10.1039/D1PY01473K
    17. Saurabh Shah, Paras Famta, Rajeev Singh Raghuvanshi, Shashi Bala Singh, Saurabh Srivastava. Lipid polymer hybrid nanocarriers: Insights into synthesis aspects, characterization, release mechanisms, surface functionalization and potential implications. Colloid and Interface Science Communications 2022, 46 , 100570. https://doi.org/10.1016/j.colcom.2021.100570
    18. Bingtao Zhao, Huimei Li, Dongshen Wang, Qian Liu, Yaxin Su. Insight into performance and mechanism of energy loss for microscale vortex separator/reactor with symmetrical multi-inlets. Powder Technology 2022, 395 , 122-132. https://doi.org/10.1016/j.powtec.2021.09.047
    19. Jesús Valdés, Jorge Luis Domínguez-Juárez, Rufino Nava, Ángeles Cuán, Carlos M. Cortés-Romero. Turbulence Enhancement and Mixing Analysis for Multi-Inlet Vortex Photoreactor for CO2 Reduction. Processes 2021, 9 (12) , 2237. https://doi.org/10.3390/pr9122237
    20. Xiangsheng Liu, Huan Meng. Consideration for the scale‐up manufacture of nanotherapeutics—A critical step for technology transfer. VIEW 2021, 2 (5) https://doi.org/10.1002/VIW.20200190
    21. Qiang-Wei Zhan, Yan Huang. Continuous and large-scale fabrication of lecithin stabilized nanoparticles with predictable size and stability using flash nano-precipitation. LWT 2021, 139 , 110558. https://doi.org/10.1016/j.lwt.2020.110558
    22. Xiangzhao Ai, Yaou Duan, Qiangzhe Zhang, Derrick Sun, Ronnie H. Fang, Ru Liu‐Bryan, Weiwei Gao, Liangfang Zhang. Cartilage‐targeting ultrasmall lipid‐polymer hybrid nanoparticles for the prevention of cartilage degradation. Bioengineering & Translational Medicine 2021, 6 (1) https://doi.org/10.1002/btm2.10187
    23. K. S. Joshy, S. Snigdha, Sabu Thomas. Nanotechnology and Its Implication in Antiviral Drug Delivery. 2021, 169-207. https://doi.org/10.1007/978-981-16-2119-2_8
    24. Hanze Hu, Chao Yang, Mingqiang Li, Dan Shao, Hai-Quan Mao, Kam W. Leong. Flash technology-based self-assembly in nanoformulation: Fabrication to biomedical applications. Materials Today 2021, 42 , 99-116. https://doi.org/10.1016/j.mattod.2020.08.019
    25. Sudeep Sudesh Pukale, Saurabh Sharma, Manu Dalela, Arihant kumar Singh, Sujata Mohanty, Anupama Mittal, Deepak Chitkara. Multi-component clobetasol-loaded monolithic lipid-polymer hybrid nanoparticles ameliorate imiquimod-induced psoriasis-like skin inflammation in Swiss albino mice. Acta Biomaterialia 2020, 115 , 393-409. https://doi.org/10.1016/j.actbio.2020.08.020
    26. Ramesh Marasini, Tuyen Duong Thanh Nguyen, Sagar Rayamajhi, Santosh Aryal. Synthesis and characterization of a tumor-seeking LyP-1 peptide integrated lipid–polymer composite nanoparticle. Materials Advances 2020, 1 (3) , 469-480. https://doi.org/10.1039/D0MA00203H
    27. Lai Jiang, Hiang Wee Lee, Say Chye Joachim Loo. Therapeutic lipid-coated hybrid nanoparticles against bacterial infections. RSC Advances 2020, 10 (14) , 8497-8517. https://doi.org/10.1039/C9RA10921H
    28. Cláudia Martins, Veeren M. Chauhan, Amjad A. Selo, Mohammad Al-Natour, Jonathan W. Aylott, Bruno Sarmento. Modelling protein therapeutic co-formulation and co-delivery with PLGA nanoparticles continuously manufactured by microfluidics. Reaction Chemistry & Engineering 2020, 5 (2) , 308-319. https://doi.org/10.1039/C9RE00395A
    29. Eshu Middha, Purnima Naresh Manghnani, Denise Zi Ling Ng, Huan Chen, Saif A. Khan, Bin Liu. Direct visualization of the ouzo zone through aggregation-induced dye emission for the synthesis of highly monodispersed polymeric nanoparticles. Materials Chemistry Frontiers 2019, 3 (7) , 1375-1384. https://doi.org/10.1039/C9QM00020H
    30. Adam Bohr, Stefano Colombo, Henrik Jensen. Future of microfluidics in research and in the market. 2019, 425-465. https://doi.org/10.1016/B978-0-12-812659-2.00016-8
    31. Marta Pacheco-Jerez, Beatriz Jurado-Sánchez. Biomimetic nanoparticles and self-propelled micromotors for biomedical applications. 2019, 1-31. https://doi.org/10.1016/B978-0-12-818433-2.00001-7
    32. Loutfy H. Madkour. Polymer nanoparticle drug-nucleic acid combinations. 2019, 241-255. https://doi.org/10.1016/B978-0-12-819777-6.00014-7
    33. Jinsong Tao, Shing Fung Chow, Ying Zheng. Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles. Acta Pharmaceutica Sinica B 2019, 9 (1) , 4-18. https://doi.org/10.1016/j.apsb.2018.11.001
    34. Zhenping Liu, James C. Hill, Rodney O. Fox, Alberto Passalacqua, Michael G. Olsen. A delayed detached eddy simulation model with low Reynolds number correction for transitional swirling flow in a multi-inlet vortex nanoprecipitation reactor. Chemical Engineering Science 2019, 193 , 66-75. https://doi.org/10.1016/j.ces.2018.08.020
    35. Li-Ju Wang, Yu-Chung Chang, Allison T. Osmanson, Jinwen Zhang, Lei Li. Facile continuous production of soy peptide nanogels via nanoscale flash desolvation for drug entrapment. International Journal of Pharmaceutics 2018, 549 (1-2) , 13-20. https://doi.org/10.1016/j.ijpharm.2018.07.044
    36. Dongfei Liu, Hongbo Zhang, Flavia Fontana, Jouni T. Hirvonen, Hélder A. Santos. Current developments and applications of microfluidic technology toward clinical translation of nanomedicines. Advanced Drug Delivery Reviews 2018, 128 , 54-83. https://doi.org/10.1016/j.addr.2017.08.003
    37. Monica Agnoletti, Adam Bohr, Kaushik Thanki, Feng Wan, Xianghui Zeng, Johan Peter Boetker, Mingshi Yang, Camilla Foged. Inhalable siRNA-loaded nano-embedded microparticles engineered using microfluidics and spray drying. European Journal of Pharmaceutics and Biopharmaceutics 2017, 120 , 9-21. https://doi.org/10.1016/j.ejpb.2017.08.001
    38. Jia Zhuang, Ronnie H. Fang, Liangfang Zhang. Preparation of Particulate Polymeric Therapeutics for Medical Applications. Small Methods 2017, 1 (9) https://doi.org/10.1002/smtd.201700147
    39. Rui Ran, Qi Sun, Thejus Baby, David Wibowo, Anton P.J. Middelberg, Chun-Xia Zhao. Multiphase microfluidic synthesis of micro- and nanostructures for pharmaceutical applications. Chemical Engineering Science 2017, 169 , 78-96. https://doi.org/10.1016/j.ces.2017.01.008
    40. Rajendran J.C. Bose, Rramaswamy Ravikumar, Vengadeshprabu Karuppagounder, Devasier Bennet, Sabarinathan Rangasamy, Rajarajan A. Thandavarayan. Lipid–polymer hybrid nanoparticle-mediated therapeutics delivery: advances and challenges. Drug Discovery Today 2017, 22 (8) , 1258-1265. https://doi.org/10.1016/j.drudis.2017.05.015
    41. Khalid M. El-Say, Hossam S. El-Sawy. Polymeric nanoparticles: Promising platform for drug delivery. International Journal of Pharmaceutics 2017, 528 (1-2) , 675-691. https://doi.org/10.1016/j.ijpharm.2017.06.052
    42. Katelyn R. Houston, Sarah M. Brosnan, Laurel M. Burk, Yueh Z. Lee, J. C. Luft, Valerie S. Ashby. Iodinated polyesters as a versatile platform for radiopaque biomaterials. Journal of Polymer Science Part A: Polymer Chemistry 2017, 55 (13) , 2171-2177. https://doi.org/10.1002/pola.28596
    43. . References. 2017, 129-143. https://doi.org/10.1002/9783527695294.part1a
    44. Adam Bohr, Johan Boetker, Yingya Wang, Henrik Jensen, Jukka Rantanen, Moritz Beck-Broichsitter. High-Throughput Fabrication of Nanocomplexes Using 3D-Printed Micromixers. Journal of Pharmaceutical Sciences 2017, 106 (3) , 835-842. https://doi.org/10.1016/j.xphs.2016.10.027
    45. Liu-Jie Zhang, Bo Wu, Wei Zhou, Cai-Xia Wang, Qian Wang, Hui Yu, Ren-Xi Zhuo, Zhi-Lan Liu, Shi-Wen Huang. Two-component reduction-sensitive lipid–polymer hybrid nanoparticles for triggered drug release and enhanced in vitro and in vivo anti-tumor efficacy. Biomaterials Science 2017, 5 (1) , 98-110. https://doi.org/10.1039/C6BM00662K
    46. Michael J. Toth, Taeyoung Kim, YongTae Kim. Robust manufacturing of lipid-polymer nanoparticles through feedback control of parallelized swirling microvortices. Lab on a Chip 2017, 17 (16) , 2805-2813. https://doi.org/10.1039/C7LC00668C
    47. Shukai Ding, Nicolas Anton, Thierry F. Vandamme, Christophe A. Serra. Microfluidic nanoprecipitation systems for preparing pure drug or polymeric drug loaded nanoparticles: an overview. Expert Opinion on Drug Delivery 2016, 13 (10) , 1447-1460. https://doi.org/10.1080/17425247.2016.1193151
    48. Phatsapong Yingchoncharoen, Danuta S. Kalinowski, Des R. Richardson, . Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come. Pharmacological Reviews 2016, 68 (3) , 701-787. https://doi.org/10.1124/pr.115.012070
    49. Taylor E. Kavanaugh, Thomas A. Werfel, Hongsik Cho, Karen A. Hasty, Craig L. Duvall. Particle-based technologies for osteoarthritis detection and therapy. Drug Delivery and Translational Research 2016, 6 (2) , 132-147. https://doi.org/10.1007/s13346-015-0234-2
    50. Brian T. Luk, Liangfang Zhang. Cell membrane-camouflaged nanoparticles for drug delivery. Journal of Controlled Release 2015, 220 , 600-607. https://doi.org/10.1016/j.jconrel.2015.07.019
    51. Zhenlong Li, Alemayehu A. Gorfe. Receptor-mediated membrane adhesion of lipid–polymer hybrid (LPH) nanoparticles studied by dissipative particle dynamics simulations. Nanoscale 2015, 7 (2) , 814-824. https://doi.org/10.1039/C4NR04834B
    52. Koen Raemdonck, Kevin Braeckmans, Jo Demeester, Stefaan C. De Smedt. Merging the best of both worlds: hybrid lipid-enveloped matrix nanocomposites in drug delivery. Chem. Soc. Rev. 2014, 43 (1) , 444-472. https://doi.org/10.1039/C3CS60299K
    53. Che-Ming J. Hu, Ronnie H. Fang, Brian T. Luk, Liangfang Zhang. Polymeric nanotherapeutics: clinical development and advances in stealth functionalization strategies. Nanoscale 2014, 6 (1) , 65-75. https://doi.org/10.1039/C3NR05444F
    54. Raquel Mejia-Ariza, Jurriaan Huskens. Formation of hybrid gold nanoparticle network aggregates by specific host–guest interactions in a turbulent flow reactor. J. Mater. Chem. B 2014, 2 (2) , 210-216. https://doi.org/10.1039/C3TB21228A
    55. Kunn Hadinoto, Ajitha Sundaresan, Wean Sin Cheow. Lipid–polymer hybrid nanoparticles as a new generation therapeutic delivery platform: A review. European Journal of Pharmaceutics and Biopharmaceutics 2013, 85 (3) , 427-443. https://doi.org/10.1016/j.ejpb.2013.07.002
    56. Jacob Weingart, Pratima Vabbilisetty, Xue-Long Sun. Membrane mimetic surface functionalization of nanoparticles: Methods and applications. Advances in Colloid and Interface Science 2013, 197-198 , 68-84. https://doi.org/10.1016/j.cis.2013.04.003
    57. Weiwei Gao, Che-Ming J. Hu, Ronnie H. Fang, Liangfang Zhang. Liposome-like nanostructures for drug delivery. Journal of Materials Chemistry B 2013, 1 (48) , 6569. https://doi.org/10.1039/c3tb21238f