Abstract
Significant endeavors can be made to develop effective drug delivery systems. Nowadays, many of these novel systems have gained attention as they focus primarily on increasing the bioavailability and bioaccessibility of several drugs to finally minimize the side effects, thus improving the treatment's efficacy. Microfluidics systems are unquestionably a superior technology, which is currently revolutionizing the current chemical and biological studies, providing diminutive chip-scale devices that offer precise dosage, target-precise delivery, and controlled release. Microfluidic systems have emerged as a promising delivery vehicle owing to their potential for defined handling and transporting of small liquid quantities. The latest microfabrication developments have been made for application to several biological systems. Here, we review the fundamentals of microfluidics and their application for local drug delivery.
Keywords: Microfluidics, local drug delivery, drug targeting, ocular delivery, brain delivery, tissue engineering.
[1]
Zhang Y, Chan HF, Leong KW. Advanced materials and processing for drug delivery: The past and the future. Adv Drug Deliv Rev 2013; 65(1): 104-20.
[http://dx.doi.org/10.1016/j.addr.2012.10.003]
[http://dx.doi.org/10.1016/j.addr.2012.10.003]
[2]
Couvreur P. Nanoparticles in drug delivery: Past, present and future. Adv Drug Deliv Rev 2013; 65(1): 21-3.
[http://dx.doi.org/10.1016/j.addr.2012.04.010] [PMID: 22580334]
[http://dx.doi.org/10.1016/j.addr.2012.04.010] [PMID: 22580334]
[3]
Singh A, Agarwal R, Diaz-Ruiz CA, et al. Nanoengineered particles for enhanced intra-articular retention and delivery of proteins. Adv Healthc Mater 2014; 3(10): 1562-1567. 1525
[http://dx.doi.org/10.1002/adhm.201400051] [PMID: 24687997]
[http://dx.doi.org/10.1002/adhm.201400051] [PMID: 24687997]
[4]
Walmsley GG, McArdle A, Tevlin R, et al. Nanotechnology in bone tissue engineering. Nanomedicine 2015; 11(5): 1253-63.
[http://dx.doi.org/10.1016/j.nano.2015.02.013]
[http://dx.doi.org/10.1016/j.nano.2015.02.013]
[5]
Fontana F, Ferreira MPA, Correia A, Hirvonen J, Santos HA. Microfluidics as a cutting-edge technique for drug delivery applications. J Drug Deliv Sci Technol 2016; 34: 76-87.
[http://dx.doi.org/10.1016/j.jddst.2016.01.010]
[http://dx.doi.org/10.1016/j.jddst.2016.01.010]
[6]
Tang Z, He C, Tian H, et al. Polymeric nanostructured materials for biomedical applications. In: Helder AS, Dongfei L, Hongboo Z, Eds. Prog Polym Sci 2016; 60: 86-128.
[http://dx.doi.org/10.1016/j.progpolymsci.2016.05.005]
[http://dx.doi.org/10.1016/j.progpolymsci.2016.05.005]
[7]
Sebastian V, Arruebo M. Microfluidic production of inorganic nanomaterials for biomedical applications.Microfluidics for pharmaceutical applications: from nano/micro systems fabrication to controlled drug delivery. New Jersey: Elsevier 2018.
[8]
Whitesides GM. The origins and the future of microfluidics. Nature 2006; 442(7101): 368-73.
[http://dx.doi.org/10.1038/nature05058]
[http://dx.doi.org/10.1038/nature05058]
[9]
Squires TM, Quake SR. Microfluidics: Fluid physics at the nanoliter scale. Rev Mod Phys 2005; 77(3): 977-1026.
[http://dx.doi.org/10.1103/RevModPhys.77.977]
[http://dx.doi.org/10.1103/RevModPhys.77.977]
[10]
Feng Q, Sun J, Jiang X. Microfluidics-mediated assembly of functional nanoparticles for cancer-related pharmaceutical applications. Nanoscale 2016; 8(25): 12430-43.
[http://dx.doi.org/10.1039/C5NR07964K]
[http://dx.doi.org/10.1039/C5NR07964K]
[11]
Elvira KSI. i Solvas Casadevall X, Wootton RCR, deMello AJ. The past, present and potential for microfluidic reactor technology in chemical synthesis. Nat Chem 2013; 5(11): 905-15.
[http://dx.doi.org/10.1038/nchem.1753] [PMID: 24153367]
[http://dx.doi.org/10.1038/nchem.1753] [PMID: 24153367]
[12]
Hughes AJ, Lin RKC, Peehl DM, Herr AE. Microfluidic integration for automated targeted proteomic assays. Proc Natl Acad Sci USA 2012; 109(16): 5972-7.
[http://dx.doi.org/10.1073/pnas.1108617109] [PMID: 22474344]
[http://dx.doi.org/10.1073/pnas.1108617109] [PMID: 22474344]
[13]
Yang J, Giessen H, Lalanne P. Simple analytical expression for the peak-frequency shifts of plasmonic resonances for sensing. Nano Lett 2015; 15(5): 3439-44.
[http://dx.doi.org/10.1021/acs.nanolett.5b00771] [PMID: 25844813]
[http://dx.doi.org/10.1021/acs.nanolett.5b00771] [PMID: 25844813]
[14]
Nguyen NT, Shaegh SAM, Kashaninejad N, Phan DT. Design, fabrication and characterization of drug delivery systems based on lab-on-a-chip technology. Adv Drug Deliv Rev 2013; 65(11-12): 1403-19.
[http://dx.doi.org/10.1016/j.addr.2013.05.008] [PMID: 23726943]
[http://dx.doi.org/10.1016/j.addr.2013.05.008] [PMID: 23726943]
[15]
Wu MH, Huang S, Lee G-B. Microfluidic cell culture systems for drug research. Lab Chip 2010; 10(8): 939.
[http://dx.doi.org/10.1039/b921695b]
[http://dx.doi.org/10.1039/b921695b]
[16]
Kang L, Chung BG, Langer R, Khademhosseini A. Microfluidics for drug discovery and development: From target selection to product lifecycle management. Drug Discov Today 2008; 13(1-2): 1-13.
[http://dx.doi.org/10.1016/j.drudis.2007.10.003] [PMID: 18190858]
[http://dx.doi.org/10.1016/j.drudis.2007.10.003] [PMID: 18190858]
[17]
Khademhosseini A, Langer R, Borenstein J, Vacanti JP. Microscale technologies for tissue engineering and biology. PNAS 2006; 103(6)
[http://dx.doi.org/10.1073/pnas.0507681102]
[http://dx.doi.org/10.1073/pnas.0507681102]
[18]
Meyvantsson I, Beebe DJ. Cell culture models in microfluidic systems. Annu Rev Anal Chem (Palo Alto, Calif) 2008; 1(1): 423-49.
[http://dx.doi.org/10.1146/annurev.anchem.1.031207.113042]
[http://dx.doi.org/10.1146/annurev.anchem.1.031207.113042]
[19]
Tirella A, Marano M, Vozzi F, Ahluwalia A. A microfluidic gradient maker for toxicity testing of bupivacaine and lidocaine. Toxicol Vitr 2008; 22(8)
[http://dx.doi.org/10.1016/j.tiv.2008.09.016]
[http://dx.doi.org/10.1016/j.tiv.2008.09.016]
[20]
Keenan TM, Folch A. Biomolecular gradients in cell culture systems. Lab Chip 2007; 8.
[PMID: 18094760]
[PMID: 18094760]
[21]
Chung BG, Choo J. Microfluidic gradient platforms for controlling cellular behavior. Electrophoresis 2010; 31(18): 3014-27.
[http://dx.doi.org/10.1002/elps.201000137] [PMID: 20734372]
[http://dx.doi.org/10.1002/elps.201000137] [PMID: 20734372]
[22]
La Van DA, Lynn DM, Langer R. Moving smaller in drug discovery and delivery. Nat Rev Drug Discov 2002; 1(1): 77-84.
[http://dx.doi.org/10.1038/nrd707]
[http://dx.doi.org/10.1038/nrd707]
[23]
Weigl BH, Bardell RL, Cabrera CR. Lab-on-a-chip for drug development. Adv Drug Deliv Rev 2003; 55(3): 349-77.
[http://dx.doi.org/10.1016/S0169-409X(02)00223-5]
[http://dx.doi.org/10.1016/S0169-409X(02)00223-5]
[24]
Rehfeldt F, Engler AJ, Eckhardt A, Ahmed F, Discher DE. Cell responses to the mechanochemical microenvironment-implications for regenerative medicine and drug delivery. Adv Drug Deliv Rev 2007; 59(13): 1329-39.
[http://dx.doi.org/10.1016/j.addr.2007.08.007] [PMID: 17900747]
[http://dx.doi.org/10.1016/j.addr.2007.08.007] [PMID: 17900747]
[25]
Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2007; 2(12): 751-60.
[http://dx.doi.org/10.1038/nnano.2007.387] [PMID: 18654426]
[http://dx.doi.org/10.1038/nnano.2007.387] [PMID: 18654426]
[26]
Kim YC, Park JH, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev 2012; 64(14): 1547-68.
[http://dx.doi.org/10.1016/j.addr.2012.04.005]
[http://dx.doi.org/10.1016/j.addr.2012.04.005]
[27]
Baker M. Tissue models: A living system on a chip. Nature 2011; 471(7340): 661-5.
[http://dx.doi.org/10.1038/471661a] [PMID: 21455183]
[http://dx.doi.org/10.1038/471661a] [PMID: 21455183]
[28]
Moraes C, Mehta G, Lesher-Perez SC, Takayama S. Organs-on-a-chip: A focus on compartmentalized microdevices. Ann Biomed Eng 2012; 40(6): 1211-27.
[http://dx.doi.org/10.1007/s10439-011-0455-6] [PMID: 22065201]
[http://dx.doi.org/10.1007/s10439-011-0455-6] [PMID: 22065201]
[29]
Champion JA, Katare YK, Mitragotri S. Particle shape: A new design parameter for micro- and nanoscale drug delivery carriers. J Control Release 2007; 121(1-2): 3-9.
[http://dx.doi.org/10.1016/j.jconrel.2007.03.022] [PMID: 17544538]
[http://dx.doi.org/10.1016/j.jconrel.2007.03.022] [PMID: 17544538]
[30]
Gañán-Calvo AM, Montanero JM, Martín-Banderas L, Flores-Mosquera M. Building functional materials for health care and pharmacy from microfluidic principles and Flow Focusing. Adv Drug Deliv Rev 2013; 65(11-12): 1447-69.
[http://dx.doi.org/10.1016/j.addr.2013.08.003] [PMID: 23954401]
[http://dx.doi.org/10.1016/j.addr.2013.08.003] [PMID: 23954401]
[31]
Tsui JH, Lee W, Pun SH, Kim J, Kim DH. Microfluidics-assisted in vitro drug screening and carrier production. Adv Drug Deliv Rev 2013; 65(11-12): 1575-88.
[http://dx.doi.org/10.1016/j.addr.2013.07.004] [PMID: 23856409]
[http://dx.doi.org/10.1016/j.addr.2013.07.004] [PMID: 23856409]
[32]
Owens DE III, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 2006; 307(1): 93-102.
[http://dx.doi.org/10.1016/j.ijpharm.2005.10.010] [PMID: 16303268]
[http://dx.doi.org/10.1016/j.ijpharm.2005.10.010] [PMID: 16303268]
[33]
Zhao CX. Multiphase flow microfluidics for the production of single or multiple emulsions for drug delivery. Adv Drug Deliv Rev 2013; 65(11-12): 1420-46.
[http://dx.doi.org/10.1016/j.addr.2013.05.009]
[http://dx.doi.org/10.1016/j.addr.2013.05.009]
[34]
Mathaes R, Winter G, Besheer A, Engert J. Non-spherical micro- and nanoparticles: Fabrication, characterization and drug delivery applications. Expert Opin Drug Deliv 2015; 12(3): 481-92.
[http://dx.doi.org/10.1517/17425247.2015.963055] [PMID: 25327886]
[http://dx.doi.org/10.1517/17425247.2015.963055] [PMID: 25327886]
[35]
Kolhar P, Anselmo AC, Gupta V, et al. Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium. Proc Natl Acad Sci USA 2013; 110(26): 10753-8.
[http://dx.doi.org/10.1073/pnas.1308345110] [PMID: 23754411]
[http://dx.doi.org/10.1073/pnas.1308345110] [PMID: 23754411]
[36]
Studart AR, Shum HC, Weitz DA. Arrested coalescence of particle-coated droplets into nonspherical supracolloidal structures. J Phys Chem B 2009; 113(12): 3914-9.
[http://dx.doi.org/10.1021/jp806795c] [PMID: 19673138]
[http://dx.doi.org/10.1021/jp806795c] [PMID: 19673138]
[37]
Shum HC, Abate AR, Lee D, et al. Droplet microfluidics for fabrication of non-spherical particles. Macromol Rapid Commun 2010; 31(2): 108-18.
[http://dx.doi.org/10.1002/marc.200900590] [PMID: 21590882]
[http://dx.doi.org/10.1002/marc.200900590] [PMID: 21590882]
[38]
Kang JS, Lee MH. Overview of therapeutic drug monitoring. Korean J Intern Med (Korean Assoc Intern Med) 2009; 24(1): 1.
[http://dx.doi.org/10.3904/kjim.2009.24.1.1]
[http://dx.doi.org/10.3904/kjim.2009.24.1.1]
[39]
Razzacki SZ, Thwar PK, Yang M, Ugaz VM, Burns MA. Integrated microsystems for controlled drug delivery. Adv Drug Deliv Rev 2004; 56(2): 185-98.
[http://dx.doi.org/10.1016/j.addr.2003.08.012] [PMID: 14741115]
[http://dx.doi.org/10.1016/j.addr.2003.08.012] [PMID: 14741115]
[40]
Liechty WB, Kryscio DR, Slaughter BV, Peppas NA. Polymers for drug delivery systems. Annu Rev Chem Biomol Eng 2010; 1(1): 149-73.
[http://dx.doi.org/10.1146/annurev-chembioeng-073009-100847] [PMID: 22432577]
[http://dx.doi.org/10.1146/annurev-chembioeng-073009-100847] [PMID: 22432577]
[41]
Sasahara K, McPhie P, Minton AP. Effect of dextran on protein stability and conformation attributed to macromolecular crowding. J Mol Biol 2003; 326(4): 1227-37.
[http://dx.doi.org/10.1016/S0022-2836(02)01443-2] [PMID: 12589765]
[http://dx.doi.org/10.1016/S0022-2836(02)01443-2] [PMID: 12589765]
[42]
Bae YH, Park K. Targeted drug delivery to tumors: Myths, reality and possibility. J Control Release 2011; 153(3): 198-205.
[http://dx.doi.org/10.1016/j.jconrel.2011.06.001]
[http://dx.doi.org/10.1016/j.jconrel.2011.06.001]
[43]
Stevenson CL, Santini JT Jr, Langer R. Reservoir-based drug delivery systems utilizing microtechnology. Adv Drug Deliv Rev 2012; 64(14): 1590-602.
[http://dx.doi.org/10.1016/j.addr.2012.02.005] [PMID: 22465783]
[http://dx.doi.org/10.1016/j.addr.2012.02.005] [PMID: 22465783]
[45]
Tanwar H, Sachdeva R. Transdermal drug delivery system: A review. Int J Pharm Sci Res 2016; 7(6)
[46]
Riahi R, Tamayol A, Shaegh SAM, Ghaemmaghami A, Dokmeci MR, Khademshosseini A. Microfluidics for advanced drug delivery systems. Curr Opin Chem Eng 2015; 7: 101-12.
[http://dx.doi.org/10.1016/j.coche.2014.12.001] [PMID: 31692947]
[http://dx.doi.org/10.1016/j.coche.2014.12.001] [PMID: 31692947]
[47]
Zhang L, Chen Q, Ma Y, Sun J. Microfluidic methods for fabrication and engineering of nanoparticle drug delivery systems. ACS Appl Bio Mater 2020; 3(1): 107-20.
[http://dx.doi.org/10.1021/acsabm.9b00853] [PMID: 35019430]
[http://dx.doi.org/10.1021/acsabm.9b00853] [PMID: 35019430]
[48]
Kaushik S, Hord AH, Denson DD, et al. Lack of pain associated with microfabricated microneedles. Anesth Analg 2001; 92(2): 502-4.
[http://dx.doi.org/10.1213/00000539-200102000-00041] [PMID: 11159258]
[http://dx.doi.org/10.1213/00000539-200102000-00041] [PMID: 11159258]
[49]
Davis SP, Landis BJ, Adams ZH, Allen MG, Prausnitz MR. Insertion of microneedles into skin: Measurement and prediction of insertion force and needle fracture force. J Biomech 2004; 37(8): 1155-63.
[http://dx.doi.org/10.1016/j.jbiomech.2003.12.010] [PMID: 15212920]
[http://dx.doi.org/10.1016/j.jbiomech.2003.12.010] [PMID: 15212920]
[50]
Tuan-Mahmood T-M, McCrudden M, Torrisi BM, et al. Microneedles for intradermal and transdermal delivery. Eur J Pharm Sci 2013; 50(5): 623-37.
[51]
McAllister DV, Wang PM, Davis SP, et al. From the cover: Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies. Proc Natl Acad Sci USA 2003; 100(24): 13755.
[52]
van der Maaden K, Jiskoot W, Bouwstra J. Microneedle technologies for (trans)dermal drug and vaccine delivery. J Control Release 2012; 161(2): 645-55.
[http://dx.doi.org/10.1016/j.jconrel.2012.01.042] [PMID: 22342643]
[http://dx.doi.org/10.1016/j.jconrel.2012.01.042] [PMID: 22342643]
[53]
Yu LM, Tay FEH, Guo DG, Xu L, Yap KL. A microfabricated electrode with hollow microneedles for ECG measurement. Sens Actuators A Phys 2009; 151(1): 17-22.
[http://dx.doi.org/10.1016/j.sna.2009.01.020]
[http://dx.doi.org/10.1016/j.sna.2009.01.020]
[54]
Tandon V, Kang WS, Spencer AJ, et al. Microfabricated infuse-withdraw micropump component for an integrated inner-ear drug-delivery platform. Biomed Microdevices 2015; 17(2): 37.
[http://dx.doi.org/10.1007/s10544-014-9923-8] [PMID: 25686902]
[http://dx.doi.org/10.1007/s10544-014-9923-8] [PMID: 25686902]
[55]
Tandon V, Kang WS, Robbins TA, et al. Microfabricated reciprocating micropump for intracochlear drug delivery with integrated drug/fluid storage and electronically controlled dosing. Lab Chip 2016; 16(5): 829-46.
[http://dx.doi.org/10.1039/C5LC01396H] [PMID: 26778829]
[http://dx.doi.org/10.1039/C5LC01396H] [PMID: 26778829]
[56]
Borenstein JT. Intracochlear drug delivery systems. Expert Opin Drug Deliv 2011; 8(9): 1161-74.
[http://dx.doi.org/10.1517/17425247.2011.588207] [PMID: 21615213]
[http://dx.doi.org/10.1517/17425247.2011.588207] [PMID: 21615213]
[57]
Swan EEL, Mescher MJ, Sewell WF, Tao SL, Borenstein JT. Inner ear drug delivery for auditory applications. Adv Drug Deliv Rev 2008; 60(15): 1583-99.
[http://dx.doi.org/10.1016/j.addr.2008.08.001] [PMID: 18848590]
[http://dx.doi.org/10.1016/j.addr.2008.08.001] [PMID: 18848590]
[59]
McCall AA, Swan EEL, Borenstein JT, Sewell WF, Kujawa SG, McKenna MJ. Drug delivery for treatment of inner ear disease: Current state of knowledge. Ear Hear 2010; 31(2): 156-65.
[http://dx.doi.org/10.1097/AUD.0b013e3181c351f2] [PMID: 19952751]
[http://dx.doi.org/10.1097/AUD.0b013e3181c351f2] [PMID: 19952751]
[60]
Pararas EEL, Borkholder DA, Borenstein JT. Microsystems technologies for drug delivery to the inner ear. Adv Drug Deliv Rev 2012; 64(14): 1650-60.
[http://dx.doi.org/10.1016/j.addr.2012.02.004] [PMID: 22386561]
[http://dx.doi.org/10.1016/j.addr.2012.02.004] [PMID: 22386561]
[61]
Lehner E, Menzel M, Gündel D, et al. Microimaging of a novel intracochlear drug delivery device in combination with cochlear implants in the human inner ear. Drug Deliv Transl Res 2021.
[PMID: 33543398]
[PMID: 33543398]
[62]
Kim ES, Gustenhoven E, Mescher MJ, et al. A microfluidic reciprocating intracochlear drug delivery system with reservoir and active dose control. Lab Chip 2014; 14(4): 710-21.
[http://dx.doi.org/10.1039/C3LC51105G] [PMID: 24302432]
[http://dx.doi.org/10.1039/C3LC51105G] [PMID: 24302432]
[63]
Sewell WF, Borenstein JT, Chen Z, et al. Development of a microfluidics-based intracochlear drug delivery device. Audiol Neurotol 2009; 14(6): 411-22.
[http://dx.doi.org/10.1159/000241898] [PMID: 19923811]
[http://dx.doi.org/10.1159/000241898] [PMID: 19923811]
[64]
Ayoob AM, Borenstein JT. The role of intracochlear drug delivery devices in the management of inner ear disease. Expert Opin Drug Deliv 2015; 12(3): 465-79.
[http://dx.doi.org/10.1517/17425247.2015.974548] [PMID: 25347140]
[http://dx.doi.org/10.1517/17425247.2015.974548] [PMID: 25347140]
[65]
Ding D, Kundukad B, Somasundar A, Vijayan S, Khan SA, Doyle PS. Design of mucoadhesive PLGA microparticles for ocular drug delivery. ACS Appl Bio Mater 2018; 1(3): 561-71.
[http://dx.doi.org/10.1021/acsabm.8b00041] [PMID: 34996190]
[http://dx.doi.org/10.1021/acsabm.8b00041] [PMID: 34996190]
[66]
Sanjay ST, Zhou W, Dou M, et al. Recent advances of controlled drug delivery using microfluidic platforms. Adv Drug Deliv Rev 2018; 128: 3-28.
[http://dx.doi.org/10.1016/j.addr.2017.09.013] [PMID: 28919029]
[http://dx.doi.org/10.1016/j.addr.2017.09.013] [PMID: 28919029]
[67]
Souto EB, Dias-Ferreira J, López-Machado A, et al. Advanced formulation approaches for ocular drug delivery: State-of-the-art and recent patents. Pharmaceutics 2019; 11(9): E460.
[http://dx.doi.org/10.3390/pharmaceutics11090460] [PMID: 31500106]
[http://dx.doi.org/10.3390/pharmaceutics11090460] [PMID: 31500106]
[68]
Lo R, Li PY, Saati S, Agrawal RN, Humayun MS, Meng E. A passive MEMS drug delivery pump for treatment of ocular diseases. Biomed Microdevices 2009; 11(5): 959-70.
[http://dx.doi.org/10.1007/s10544-009-9313-9] [PMID: 19396548]
[http://dx.doi.org/10.1007/s10544-009-9313-9] [PMID: 19396548]
[69]
Li PY, Shih J, Lo R, et al. An electrochemical intraocular drug delivery device. Sens Actuators A Phys 2008; 143(1): 41-8.
[http://dx.doi.org/10.1016/j.sna.2007.06.034]
[http://dx.doi.org/10.1016/j.sna.2007.06.034]
[70]
Gensler H, Sheybani R, Li PY, Mann RL, Meng E. An implantable MEMS micropump system for drug delivery in small animals. Biomed Microdevices 2012; 14(3): 483-96.
[http://dx.doi.org/10.1007/s10544-011-9625-4] [PMID: 22273985]
[http://dx.doi.org/10.1007/s10544-011-9625-4] [PMID: 22273985]
[71]
Pirmoradi FN, Jackson JK, Burt HM, Chiao M. On-demand controlled release of docetaxel from a battery-less MEMS drug delivery device. Lab Chip 2011; 11(16): 2744-52.
[http://dx.doi.org/10.1039/c1lc20134d] [PMID: 21698338]
[http://dx.doi.org/10.1039/c1lc20134d] [PMID: 21698338]
[72]
Filipe HP, Paradiso P, Valente ARB, et al. Microfluidic in vitro drug release from contact lens materials. Acta Ophthalmol 2015; 93: S255.
[http://dx.doi.org/10.1111/j.1755-3768.2015.0578]
[http://dx.doi.org/10.1111/j.1755-3768.2015.0578]
[73]
Amoozgar B, Wei X, Hui Lee J, et al. A novel flexible microfluidic meshwork to reduce fibrosis in glaucoma surgery. PLoS One 2017; 12(3): e0172556.
[http://dx.doi.org/10.1371/journal.pone.0172556] [PMID: 28301490]
[http://dx.doi.org/10.1371/journal.pone.0172556] [PMID: 28301490]
[74]
Oddo A, Peng B, Tong Z, et al. Advances in Microfluidic Blood-Brain Barrier (BBB). Models Trends Biotechnol 2019; 37(12): 1295-314.
[http://dx.doi.org/10.1016/j.tibtech.2019.04.006] [PMID: 31130308]
[http://dx.doi.org/10.1016/j.tibtech.2019.04.006] [PMID: 31130308]
[75]
Zhao Y, Demirci U, Chen Y, Chen P. Multiscale brain research on a microfluidic chip. Lab Chip 2020; 20(9): 1531-43.
[http://dx.doi.org/10.1039/C9LC01010F]
[http://dx.doi.org/10.1039/C9LC01010F]
[76]
Wilhelm I, Krizbai IA. In vitro models of the blood-brain barrier for the study of drug delivery to the brain. Mol Pharm 2014; 11(7): 1949-63.
[http://dx.doi.org/10.1021/mp500046f] [PMID: 24641309]
[http://dx.doi.org/10.1021/mp500046f] [PMID: 24641309]
[77]
Lee CS, Leong KW. Advances in microphysiological blood-brain barrier (BBB) models towards drug delivery. Curr Opin Biotechnol 2020; 66: 78-87.
[http://dx.doi.org/10.1016/j.copbio.2020.06.009]
[http://dx.doi.org/10.1016/j.copbio.2020.06.009]
[78]
van der Helm MW, van der Meer AD, Eijkel JCT, van den Berg A, Segerink LI. Microfluidic organ-on-chip technology for blood-brain barrier research. Tissue Barriers 2016; 4(1): e1142493.
[http://dx.doi.org/10.1080/21688370.2016.1142493] [PMID: 27141422]
[http://dx.doi.org/10.1080/21688370.2016.1142493] [PMID: 27141422]
[79]
Neeves KB, Lo CT, Foley CP, Saltzman WM, Olbricht WL. Fabrication and characterization of microfluidic probes for convection enhanced drug delivery. J Control Release 2006; 111(3): 252-62.
[http://dx.doi.org/10.1016/j.jconrel.2005.11.018] [PMID: 16476500]
[http://dx.doi.org/10.1016/j.jconrel.2005.11.018] [PMID: 16476500]
[80]
Foley CP, Nishimura N, Neeves KB, Schaffer CB, Olbricht WL. Flexible microfluidic devices supported by biodegradable insertion scaffolds for convection-enhanced neural drug delivery. Biomed Microdevices 2009; 11(4): 915-24.
[http://dx.doi.org/10.1007/s10544-009-9308-6] [PMID: 19353271]
[http://dx.doi.org/10.1007/s10544-009-9308-6] [PMID: 19353271]
[81]
Wang X, Hou Y, Ai X, et al. Potential applications of microfluidics based blood brain barrier (BBB)-on-chips for in vitro drug development. Biomed Pharmacother 2020; 132: 110822.
[http://dx.doi.org/10.1016/j.biopha.2020.110822]
[http://dx.doi.org/10.1016/j.biopha.2020.110822]
[82]
Walter FR, Valkai S, Kincses A, et al. A versatile lab-on-a-chip tool for modeling biological barriers. Sens Actuators B Chem 2016; 222: 1209-19.
[http://dx.doi.org/10.1016/j.snb.2015.07.110]
[http://dx.doi.org/10.1016/j.snb.2015.07.110]
[83]
Marino A, Tricinci O, Battaglini M, et al. A 3D Real-scale, biomimetic, and biohybrid model of the blood-brain barrier fabricated through two-photon lithography. Small 2018; 14(6): 1702959.
[http://dx.doi.org/10.1002/smll.201702959] [PMID: 29239532]
[http://dx.doi.org/10.1002/smll.201702959] [PMID: 29239532]
[84]
Maoz BM, Herland A, FitzGerald EA, et al. A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells. Nat Biotechnol 2018; 36(9): 865-74.
[http://dx.doi.org/10.1038/nbt.4226] [PMID: 30125269]
[http://dx.doi.org/10.1038/nbt.4226] [PMID: 30125269]
[85]
Bang S, Lee S-R, Ko J, et al. A low permeability microfluidic blood-brain barrier platform with direct contact between perfusable vascular network and astrocytes. Sci Rep 2017; 7(1): 1-10.
[http://dx.doi.org/10.1038/s41598-017-07416-0]
[http://dx.doi.org/10.1038/s41598-017-07416-0]
[86]
Bobo RH, Laske DW, Akbasak A, Morrison PF, Dedrick RL, Oldfield EH. Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci USA 1994; 91(6): 2076-80.
[http://dx.doi.org/10.1073/pnas.91.6.2076] [PMID: 8134351]
[http://dx.doi.org/10.1073/pnas.91.6.2076] [PMID: 8134351]
[87]
Szarowski DH, Andersen MD, Retterer S, et al. Brain responses to micro-machined silicon devices. Brain Res 2003; 983(1-2): 23-35.
[http://dx.doi.org/10.1016/S0006-8993(03)03023-3] [PMID: 12914963]
[http://dx.doi.org/10.1016/S0006-8993(03)03023-3] [PMID: 12914963]
[88]
Rousche PJ, Pellinen DS, Pivin DP Jr, Williams JC, Vetter RJ, Kipke DR. Flexible polyimide-based intracortical electrode arrays with bioactive capability. IEEE Trans Biomed Eng 2001; 48(3): 361-71.
[http://dx.doi.org/10.1109/10.914800] [PMID: 11327505]
[http://dx.doi.org/10.1109/10.914800] [PMID: 11327505]
[89]
Subbaroyan J, Martin DC, Kipke DR. A finite-element model of the mechanical effects of implantable microelectrodes in the cerebral cortex. J Neural Eng 2005; 2(4): 103-13.
[http://dx.doi.org/10.1088/1741-2560/2/4/006] [PMID: 16317234]
[http://dx.doi.org/10.1088/1741-2560/2/4/006] [PMID: 16317234]
[90]
Uguz I, Proctor CM, Curto VF, et al. A microfluidic ion pump for in vivo drug delivery. Adv Mater 2017; 29(27): 1701217.
[http://dx.doi.org/10.1002/adma.201701217] [PMID: 28503731]
[http://dx.doi.org/10.1002/adma.201701217] [PMID: 28503731]
[91]
Hassan S, Zhang YS. Microfluidic technologies for local drug delivery. In: Helder AS, Dongfei L, Hongboo Z, Eds. Microfluidics for pharmaceutical applications: from nano/micro systems fabrication to controlled drug delivery. New Jersey: Elsevier 2019; pp. 281-305.
[http://dx.doi.org/10.1016/B978-0-12-812659-2.00010-7]
[http://dx.doi.org/10.1016/B978-0-12-812659-2.00010-7]
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