The Application of Microfluidics in Preparing Nano Drug Delivery Systems
Authors: Yen Tran Thi Hai , Linh Dang Thuy , Minh Hue Pham Thi 
Published: June 2019

Microfluidics is an emerging and promising interdisciplinary technology which offers powerful platforms for precise production of novel functional materials (e.g., emulsion droplets, microcapsules, and nanoparticles as drug delivery vehicles) as well as high-throughput analyses (e.g., bioassays and diagnostics). Microfluidics has recently appeared as a new method of manufacturing nanostructures, which allows for reproducible mixing in miliseconds on the nanoliter scale. This review first describes the fundamentals of microfluidics and then introduces the recent advances in making nanostructures for pharmaceutical applications including nano liposomes, polymer nanoparticles and nano polymerosomes.
Keywords
Microfluidics, drug nanocarrier, nano liposomes, polymer nanoparticles, polymerosomes.
References
[1] Nguyễn Thanh Hải, Bùi Thanh Tùng, Phạm Thị Minh Huệ, Phỏng sinh học trong y dược học – Hướng nghiên cứu cần đẩy mạnh, Tạp chí Khoa học ĐHQGHN, Khoa học Y Dược. 33(1) (2017) 1-4. https://doi.org/10.25073/2588-1132/vnumps.4070.[2] Plug & Play Microfluidics. http://www.elveflow.com (truy cập ngày 05/08/2017).[3] L.Capretto, D. Carugo, S. Mazzitelli et al., Microfluidic and lab-on-a-chip preparation routes for organic nanoparticles and vesicular systems fornanomedicine applications, Advanced Drug Delivery Reviews. 65(11–12) (2013) 1496-1532. https://doi.org/10.1016/j.addr.2013.08.002.[4] Renolds number. https://neutrium.net/fluid_flow/reynolds-number/ (truy cập ngày 05/08/2017).[5] G.T. Vladisavljević et al., Industrial lab-on-a-chip: Design, applications and scale-up for drug discovery and delivery, Advanced Drug Delivery Reviews. 65(11–12) (2013) 1626-1663.[6] J.C. McDonald and G.M. Whitesides. Poly (dimethylsiloxane) as a Material for Fabricating Microfluidic Devices, Accounts of Chemical Research. 35 (2002) 491–499.[7] K. Ren, J. Zhou, H. Wu, Materials for Microfluidic Chip Fabrication, Accounts of chemical research. 46 (11) (2013) 2396–2406.[8] Y.Chen, L. Zang, G. Chen. Fabrication, modification, and application of poly (methyl methacrylate) microfluidic chips, Electrophoresis. 29 (2008) 1801–1814.[9] Y.P. Patil, S. Jadhav. Novel methods for liposome preparation, Chemistry and Physics of Lipids. 177 (2014) 8-18. [10] B. Yu et al. Microfluidic Methods for Production of Liposomes, Methods in Enzymology. 465 (2009) 129-141.[11] D.B.Weibel and G.M.Whitesides. Applications of microfluidics in chemical biology, Current Opinion in Chemical Biology. 10(6) (2006) 584-591.[12] Trần Thị Hải Yến. Liposome - hệ vận chuyển thuốc tiên tiến trong công nghệ dược phẩm, Tạp chí dược và thông tin thuốc. 4(4) (2013) 146-152.[13] T.M. Allen, P.R.Cullis. Liposomal drug delivery systems: From concept to clinical applications, Advanced Drug Delivery Reviews. 65(1) (2012) 36-48. https://doi.org/10.1016/j.addr.2012.09.037.[14] D. Carugo, E. Botaro, J. Owen et al., Liposome production by microﬂuidics: potential and limiting factors, Nature Scientific Reports. 6(1) (2016) 25876. [15] S. Joshi, T.H. Mariam, B.R. Carla et al., Microfluidics based manufacture of liposomes simultaneously entrapping hydrophilic and lipophilic drugs, International Journal of Pharmaceutics. 514(1) (2016) 160-168. https://doi.org/10.1016/j.ijpharm.2016.09.027.[16] D.M. Dykxhoorn and J.Lieberman. Knocking down disease with siRNAs, Cell, 126 (2006) 231–235.[17] J. Kurreck. Antisense technologies. Improvement through novel chemical modifications, Eur. J. Biochem, 270 (2003) 1628–1644.[18] C.G. Koh, X. Zhang, S. Liu et al. Delivery of antisense oligodeoxyribonucleotide lipopolyplex nanoparticles assembled by microfluidic hydrodynamic focusing, Journal of Controlled Release. 141 (2009) 62–69.[19] Trần Thị Hải Yến, Vũ Thị Hương, Phạm Thị Minh Huệ, Bào chế liposome indomethacin bằng phương pháp vi dòng chảy, Tạp chí Dược và Thông tin thuốc. 7(4-5) (2016) 36-40.[20] K.M.El-Say and H.S. El-Sawy. Polymeric nanoparticles: Promising platform for drug delivery, International Journal of Pharmaceutics. 528(1–2) (2017) 675-691.[21] A. Kumari, S.K. Yadav, S.C. Yadav et al., Biodegradable polymeric nanoparticles based drug delivery systems, Colloids and Surfaces B: Biointerfaces. 75(1) (2010) 1–18.[22] I.C. Crucho, M.T. Barros. Polymeric nanoparticles: A study on the preparation variables and characterization methods, Materials Science and Engineering. 80 (2017) 771-784. https://doi.org/10.1016/j.msec.2017.06.004[23] Phạm Thị Minh Huệ, Nguyễn Thanh Hải. Liposome, phytosome- Phỏng sinh học trong bào chế, nhà xuất bản Đại học Quốc gia Hà Nội, 2017.[24] T. Baby, L. Yun, P.J. Midleberg et.al., Fundamental studies on throughput capacities of hydrodynamic flow-focusing microfluidics for producing monodisperse polymer nanoparticles, Chemical Engineering Science. 169 (2017) 128-139. https://doi.org/10.1016/j.ces.2017.04.046Get rights and content.[25] H.K. Makadia and S.J. Siegel. Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier, Polymers, 3, (2011) 1377-1397.[26] P. Baipaywad, N. Venkatesan, B.V. Betavegi. Size-Controlled Synthesis, Characterization, and Cytotoxicity Study of Monodisperse Poly(dimethylsiloxane) Nanoparticles', Journal of Industrial and Engineering Chemistry. 53 (2017) 177-182. https://doi.org/10.1016/j.jiec.2017.04.023.[27] R.Ran, Q. Sun, T. Baby et al., Multiphase microfluidic synthesis of micro- and nanostructures. for pharmaceutical applications, Chemical Engineering Science. 169 (2017) 78-96. https://doi.org/10.1016/j.ces.2017.01.008.[28] J.Sun, Y. Xiangnuy, M. Li et al., A microfluidic origami chip for synthesis of functionalized polymeric nanoparticles, Nanoscale. 5 (2013) 5262–5265.[29] R. Karnik, F. Gu, P. Basto et al., Microfluidic platform for controlled synthesis of polymeric Nanoparticles, Nano Lett. 8 (2008) 2906–2912.[30] M.Rhee, P.M. Valencia, M.I. Rodrigues et.al. Synthesis of size-tunable polymeric nanoparticles enabled by 3D hydrodynamic flow focusing in single-layer microchannels, Adv. Mater. 23 (2011) H79–H83.[31] J.M. Lim, N. Bertrand, P.M. Valencia et.al., Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D flow focusing towards in vivo study, Nanomedicine: Nanotechnology, Biology and Medicine. 10 (2014) 401–409.[32] M.Mohammadi, R. Mohamad, A, Khalil et al., Biocompatible Polymersomes-based Cancer Theranostics: Towards Multifunctional Nanomedicine, International Journal of Pharmaceutics. 519(1-2) (2017) 287-303. https://doi.org/10.1016/j.ijpharm.2017.01.037.[33] H.Y.Chang, Y.J.Sheng, H.K.Tsao. Structural and mechanical characteristics of Polymersomes, Soft Matter. 10 (2014) 6373–6381.[34] R. Rastogi, S. Anard, V. Koul. Flexible polymerosomes-An alternative vehicle for topical delivery, Colloids and Surfaces B: Biointerfaces, 72(1) (2009) 161-166. https://doi.org/10.1016/j.colsurfb.2009.03.022.[35] L. Brown, S.L. McAthur, P.C. Wright et al., Polymersome production on a microfluidic platform using pH sensitive block copolymers, The Royal Society of Chemistry. 10 (2010) 1922–1928.[36] J.S. Lee, J. Feijen. Polymersomes for drug delivery: Design, formation and characterization, Journal of Controlled Release. 161(2) (2012) 473-483.[37] J. Thiele, D. Steimhauser, T. Pfohl et al., Preparation of Monodisperse Block Copolymer Vesicles via Flow Focusing in Microfluidics, Langmuir. 26(9) (2010) 6860–6863.[38] P.R. Makgwane and S.S. Ray. Synthesis of Nanomaterials by Continuous-Flow Microfluidics: A Review, Journal of Nanoscience and Nanotechnology. 14(2) (2014) 1338-1363.[39] M. Lu, A. Ozcelic, C.L. Grigsby et al., Microfluidic hydrodynamic focusing for synthesis of nanomaterials, Nano Today. 11(6) (2016) 778-792. https://doi.org/10.1016/j.nantod.2016.10.006.