Microfluidics for the Production of Nanomedicines: Considerations for Polymer and Lipid-based Systems

Author(s): Sarah Streck, Linda Hong, Ben J. Boyd, Arlene McDowell*.

Journal Name: Pharmaceutical Nanotechnology

Volume 7 , Issue 6 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Microfluidics is becoming increasingly of interest as a superior technique for the synthesis of nanoparticles, particularly for their use in nanomedicine. In microfluidics, small volumes of liquid reagents are rapidly mixed in a microchannel in a highly controlled manner to form nanoparticles with tunable and reproducible structure that can be tailored for drug delivery. Both polymer and lipid-based nanoparticles are utilized in nanomedicine and both are amenable to preparation by microfluidic approaches.

Aim: Therefore, the purpose of this review is to collect the current state of knowledge on the microfluidic preparation of polymeric and lipid nanoparticles for pharmaceutical applications, including descriptions of the main synthesis modalities. Of special interest are the mechanisms involved in nanoparticle formation and the options for surface functionalisation to enhance cellular interactions.

Conclusion: The review will conclude with the identification of key considerations for the production of polymeric and lipid nanoparticles using microfluidic approaches.

Keywords: Droplets, lipid, liposomes, microfluidics, nanoparticles, PLGA polymer.

[1]
Valencia PM, Farokhzad OC, Karnik R, Langer R. Microfluidic technologies for accelerating the clinical translation of nanoparticles. Nat Nanotechnol 2012; 7(10): 623-9.
[http://dx.doi.org/10.1038/nnano.2012.168] [PMID: 23042546]
[2]
Khan IU, Serra CA, Anton N, Vandamme TF. Production of nanoparticle drug delivery systems with microfluidics tools. Expert Opin Drug Deliv 2015; 12(4): 547-62.
[http://dx.doi.org/10.1517/17425247.2015.974547] [PMID: 25345543]
[3]
Whitesides GM. The origins and the future of microfluidics. Nature 2006; 442(7101): 368-73.
[http://dx.doi.org/10.1038/nature05058] [PMID: 16871203]
[4]
Valencia PM, Basto PA, Zhang L, et al. Single-step assembly of homogenous lipid-polymeric and lipid-quantum dot nanoparticles enabled by microfluidic rapid mixing. ACS Nano 2010; 4(3): 1671-9.
[http://dx.doi.org/10.1021/nn901433u] [PMID: 20166699]
[5]
Kang H, DeLong R, Fisher MH, Juliano RL. Tat-conjugated PAMAM dendrimers as delivery agents for antisense and siRNA oligonucleotides. Pharm Res 2005; 22(12): 2099-106.
[http://dx.doi.org/10.1007/s11095-005-8330-5] [PMID: 16184444]
[6]
Williams MS, Longmuir KJ, Yager P. A practical guide to the staggered herringbone mixer. Lab Chip 2008; 8(7): 1121-9.
[http://dx.doi.org/10.1039/b802562b] [PMID: 18584088]
[7]
Jafarifar E, Hajialyani M, Akbari M, Rahimi M, Shokoohinia Y, Fattahi A. Preparation of a reproducible long-acting formulation of risperidone-loaded PLGA microspheres using microfluidic method. Pharm Dev Technol 2017; 22(6): 836-43.
[http://dx.doi.org/10.1080/10837450.2016.1221426] [PMID: 27494230]
[8]
Othman R, Vladisavljević GT, Hemaka BHC, Nagy ZK. Production of polymeric nanoparticles by micromixing in a co-flow microfluidic glass capillary device. Chem Eng J 2015; 280: 316-29.
[http://dx.doi.org/10.1016/j.cej.2015.05.083]
[9]
Kang X, Luo C, Wei Q, et al. Mass production of highly monodisperse polymeric nanoparticles by parallel flow focusing system. Microfluid Nanofluidics 2013; 15(3): 337-45.
[http://dx.doi.org/10.1007/s10404-013-1152-6]
[10]
Bramosanti M, Chronopoulou L, Grillo F, Valletta A, Palocci C. Microfluidic-assisted nanoprecipitation of antiviral-loaded polymeric nanoparticles. Colloids Surf A Physicochem Eng Asp 2017; 532: 369-76.
[http://dx.doi.org/10.1016/j.colsurfa.2017.04.062]
[11]
Ortiz de Solorzano I, Uson L, Larrea A, Miana M, Sebastian V, Arruebo M. Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing. Int J Nanomedicine 2016; 11: 3397-416.
[http://dx.doi.org/10.2147/IJN.S108812] [PMID: 27524896]
[12]
Min KI, Im DJ, Lee HJ, Kim DP. Three-dimensional flash flow microreactor for scale-up production of monodisperse PEG-PLGA nanoparticles. Lab Chip 2014; 14(20): 3987-92.
[http://dx.doi.org/10.1039/C4LC00700J] [PMID: 25133684]
[13]
Laulicht B, Cheifetz P, Mathiowitz E, Tripathi A. Evaluation of continuous flow nanosphere formation by controlled microfluidic transport. Langmuir 2008; 24(17): 9717-26.
[http://dx.doi.org/10.1021/la8009332] [PMID: 18681411]
[14]
Liu K, Zhu Z, Wang X, et al. Microfluidics-based single-step preparation of injection-ready polymeric nanosystems for medical imaging and drug delivery. Nanoscale 2015; 7(40): 16983-93.
[http://dx.doi.org/10.1039/C5NR03543K] [PMID: 26415866]
[15]
Kim Y, Lee Chung B, Ma M, et al. Mass production and size control of lipid-polymer hybrid nanoparticles through controlled microvortices. Nano Lett 2012; 12(7): 3587-91.
[http://dx.doi.org/10.1021/nl301253v] [PMID: 22716029]
[16]
Sun J, Zhang L, Wang J, et al. Tunable rigidity of (polymeric core)-(lipid shell) nanoparticles for regulated cellular uptake. Adv Mater 2015; 27(8): 1402-7.
[http://dx.doi.org/10.1002/adma.201404788] [PMID: 25529120]
[17]
Jahn A, Vreeland WN, Gaitan M, Locascio LE. Controlled vesicle self-assembly in microfluidic channels with hydrodynamic focusing. J Am Chem Soc 2004; 126(9): 2674-5.
[http://dx.doi.org/10.1021/ja0318030] [PMID: 14995164]
[18]
Kastner E, Kaur R, Lowry D, Moghaddam B, Wilkinson A, Perrie Y. High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization. Int J Pharm 2014; 477(1-2): 361-8.
[http://dx.doi.org/10.1016/j.ijpharm.2014.10.030] [PMID: 25455778]
[19]
Lim JM, Bertrand N, Valencia PM, et al. Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D flow focusing towards in vivo study. Nanomedicine 2014; 10(2): 401-9.
[http://dx.doi.org/10.1016/j.nano.2013.08.003] [PMID: 23969105]
[20]
Wang JT, Wang J, Han JJ. Fabrication of advanced particles and particle-based materials assisted by droplet-based microfluidics. Small 2011; 7(13): 1728-54.
[http://dx.doi.org/10.1002/smll.201001913] [PMID: 21618428]
[21]
Utada AS, Chu LY, Fernandez-Nieves A, Link DR, Holtze C, Weitz DA. Dripping, jetting, drops, and wetting: the magic of microfluidics. MRS Bull 2007; 32(9): 702-8.
[http://dx.doi.org/10.1557/mrs2007.145]
[22]
Anna SL, Bontoux N, Stone HA. Formation of dispersions using “flow focusing” in microchannels. Appl Phys Lett 2003; 82(3): 364-6.
[http://dx.doi.org/10.1063/1.1537519]
[23]
Baroud CN, Gallaire F, Dangla R. Dynamics of microfluidic droplets. Lab Chip 2010; 10(16): 2032-45.
[http://dx.doi.org/10.1039/c001191f] [PMID: 20559601]
[24]
Capretto L, Carugo D, Mazzitelli S, Nastruzzi C, Zhang X. Microfluidic and lab-on-a-chip preparation routes for organic nanoparticles and vesicular systems for nanomedicine applications. Adv Drug Deliv Rev 2013; 65(11-12): 1496-532.
[http://dx.doi.org/10.1016/j.addr.2013.08.002] [PMID: 23933616]
[25]
Du Y, Zhang Z, Yim C, Lin M, Cao X. A simplified design of the staggered herringbone micromixer for practical applications. Biomicrofluidics 2010; 4(2)024105
[http://dx.doi.org/10.1063/1.3427240] [PMID: 20697584]
[26]
Stroock AD, Dertinger SK, Ajdari A, Mezic I, Stone HA, Whitesides GM. Chaotic mixer for microchannels. Science 2002; 295(5555): 647-51.
[http://dx.doi.org/10.1126/science.1066238] [PMID: 11809963]
[27]
Feng Q, Liu J, Li X, et al. One-step microfluidic synthesis of nanocomplex with tunable rigidity and acid-switchable surface charge for overcoming drug resistance. Small 2017; 13(9)1603109
[http://dx.doi.org/10.1002/smll.201603109] [PMID: 27943612]
[28]
Zhang L, Feng Q, Wang J, et al. Microfluidic synthesis of hybrid nanoparticles with controlled lipid layers: Understanding flexibility-regulated cell-nanoparticle interaction. ACS Nano 2015; 9(10): 9912-21.
[http://dx.doi.org/10.1021/acsnano.5b05792] [PMID: 26448362]
[29]
Leung MHM, Shen AQ. Microfluidic assisted nanoprecipitation of PLGA nanoparticles for curcumin delivery to leukemia jurkat cells. Langmuir 2018; 34(13): 3961-70.
[http://dx.doi.org/10.1021/acs.langmuir.7b04335] [PMID: 29544247]
[30]
Donno R, Gennari A, Lallana E, et al. Nanomanufacturing through microfluidic-assisted nanoprecipitation: advanced analytics and structure-activity relationships. Int J Pharm 2017; 534(1-2): 97-107.
[http://dx.doi.org/10.1016/j.ijpharm.2017.10.006] [PMID: 29017804]
[31]
Kolishetti N, Dhar S, Valencia PM, et al. Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy. Proc Natl Acad Sci 2010; 107(42): 17939-44.
[http://dx.doi.org/10.1073/pnas.1011368107] [PMID: 20921363]
[32]
Li Y, Huang X, Lee RJ, et al. Synthesis of polymer-lipid nanoparticles by microfluidic focusing for siRNA delivery. Molecules 2016; 21(10)E1314
[http://dx.doi.org/10.3390/molecules21101314] [PMID: 27763492]
[33]
Belliveau NM, Huft J, Lin PJ, et al. Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Mol Ther Nucleic Acids 2012; 1e37
[http://dx.doi.org/10.1038/mtna.2012.28] [PMID: 23344179]
[34]
Zhigaltsev IV, Belliveau N, Hafez I, et al. Bottom-up design and synthesis of limit size lipid nanoparticle systems with aqueous and triglyceride cores using millisecond microfluidic mixing. Langmuir 2012; 28(7): 3633-40.
[http://dx.doi.org/10.1021/la204833h] [PMID: 22268499]
[35]
Joshi S, Hussain MT, Roces CB, et al. Microfluidics based manufacture of liposomes simultaneously entrapping hydrophilic and lipophilic drugs. Int J Pharm 2016; 514(1): 160-8.
[http://dx.doi.org/10.1016/j.ijpharm.2016.09.027] [PMID: 27863660]
[36]
Lim J-M, Swami A, Gilson LM, et al. Ultra-high throughput synthesis of nanoparticles with homogeneous size distribution using a coaxial turbulent jet mixer. ACS Nano 2014; 8(6): 6056-65.
[http://dx.doi.org/10.1021/nn501371n] [PMID: 24824296]
[37]
Xie H, Smith JW. Fabrication of PLGA nanoparticles with a fluidic nanoprecipitation system. J Nanobiotechnology 2010; 8: 18.
[http://dx.doi.org/10.1186/1477-3155-8-18] [PMID: 20707919]
[38]
Amoyav B, Benny O. Controlled and tunable polymer particles’ production using a single microfluidic device. Appl Nanosci 2018; 8(4): 905-14.
[http://dx.doi.org/10.1007/s13204-018-0790-0]
[39]
Hood RR, Vreeland WN, DeVoe DL. Microfluidic remote loading for rapid single-step liposomal drug preparation. Lab Chip 2014; 14(17): 3359-67.
[http://dx.doi.org/10.1039/C4LC00390J] [PMID: 25003823]
[40]
Baby T, Liu Y, Middelberg APJ, Zhao C-X. Fundamental studies on throughput capacities of hydrodynamic flow-focusing microfluidics for producing monodisperse polymer nanoparticles. Chem Eng Sci 2017; 169: 128-39.
[http://dx.doi.org/10.1016/j.ces.2017.04.046]
[41]
Toth MJ, Kim T, Kim Y. Robust manufacturing of lipid-polymer nanoparticles through feedback control of parallelized swirling microvortices. Lab Chip 2017; 17(16): 2805-13.
[http://dx.doi.org/10.1039/C7LC00668C] [PMID: 28726923]
[42]
Balbino TA, Azzoni AR, de la Torre LG. Microfluidic devices for continuous production of pDNA/cationic liposome complexes for gene delivery and vaccine therapy. Colloids Surf B Biointerfaces 2013; 111: 203-10.
[http://dx.doi.org/10.1016/j.colsurfb.2013.04.003] [PMID: 23811421]
[43]
Kim H, Sung J, Chang Y, Alfeche A, Leal C. Microfluidics synthesis of gene silencing cubosomes. ACS Nano 2018; 12(9): 9196-205.
[http://dx.doi.org/10.1021/acsnano.8b03770] [PMID: 30081623]
[44]
Xu J, Zhang S, Machado A, et al. Controllable microfluidic production of drug-loaded PLGA nanoparticles using partially water-miscible mixed solvent microdroplets as a precursor. Sci Rep 2017; 7(1): 4794.
[http://dx.doi.org/10.1038/s41598-017-05184-5] [PMID: 28684775]
[45]
Karnik R, Gu F, Basto P, et al. Microfluidic platform for controlled synthesis of polymeric nanoparticles. Nano Lett 2008; 8(9): 2906-12.
[http://dx.doi.org/10.1021/nl801736q] [PMID: 18656990]
[46]
Kastner E, Verma V, Lowry D, Perrie Y. Microfluidic-controlled manufacture of liposomes for the solubilisation of a poorly water soluble drug. Int J Pharm 2015; 485(1-2): 122-30.
[http://dx.doi.org/10.1016/j.ijpharm.2015.02.063] [PMID: 25725309]
[47]
Ghazal A, Gontsarik M, Kutter JP, et al. Direct monitoring of calcium-triggered phase transitions in cubosomes using small-angle X-ray scattering combined with microfluidics. J Appl Cryst 2016; 49(6): 2005-14.
[http://dx.doi.org/10.1107/S1600576716014199]
[48]
Iliescu C, Taylor H, Avram M, Miao J, Franssila S. A practical guide for the fabrication of microfluidic devices using glass and silicon. Biomicrofluidics 2012; 6(1): 16505-16.
[http://dx.doi.org/10.1063/1.3689939] [PMID: 22662101]
[49]
Sesen M, Alan T, Neild A. Microfluidic on-demand droplet merging using surface acoustic waves. Lab Chip 2014; 14(17): 3325-33.
[http://dx.doi.org/10.1039/C4LC00456F] [PMID: 24972001]
[50]
Leester-Schädel MLT, Jürgens F, Ritcher C, Lorenz T. Fabrication of microfluidic devices. In: Dietzel A. Microsystems for pharmatechnology. 1st ed. Springer International Publishing: Switzerland 2016; pp. 23-57.
[http://dx.doi.org/10.1007/978-3-319-26920-7_2]
[51]
Bottaro E, Nastruzzi C. “Off-the-shelf” microfluidic devices for the production of liposomes for drug delivery. Mater Sci Eng C 2016; 64: 29-33.
[http://dx.doi.org/10.1016/j.msec.2016.03.056] [PMID: 27127025]
[52]
Kamaly N, Fredman G, Fojas JJ, et al. Targeted interleukin-10 nanotherapeutics developed with a microfluidic chip enhance resolution of inflammation in advanced atherosclerosis. ACS Nano 2016; 10(5): 5280-92.
[http://dx.doi.org/10.1021/acsnano.6b01114] [PMID: 27100066]
[53]
Leng J, Joanicot M, Ajdari A. Microfluidic exploration of the phase diagram of a surfactant/water binary system. Langmuir 2007; 23(5): 2315-7.
[http://dx.doi.org/10.1021/la063169k] [PMID: 17266344]
[54]
Lee JN, Park C, Whitesides GM. Solvent compatibility of poly(dimethylsiloxane)-based microfluidic devices. Anal Chem 2003; 75(23): 6544-54.
[http://dx.doi.org/10.1021/ac0346712] [PMID: 14640726]
[55]
Ren K, Zhou J, Wu H. Materials for microfluidic chip fabrication. Acc Chem Res 2013; 46(11): 2396-406.
[http://dx.doi.org/10.1021/ar300314s] [PMID: 24245999]
[56]
Zilio C, Sola L, Damin F, Faggioni L, Chiari M. Universal hydrophilic coating of thermoplastic polymers currently used in microfluidics. Biomed Microdevices 2014; 16(1): 107-14.
[http://dx.doi.org/10.1007/s10544-013-9810-8] [PMID: 24037663]
[57]
Jena RK, Yue CY. Cyclic olefin copolymer based microfluidic devices for biochip applications: Ultraviolet surface grafting using 2-methacryloyloxyethyl phosphorylcholine. Biomicrofluidics 2012; 6(1): 12822-.
[http://dx.doi.org/10.1063/1.3682098] [PMID: 22662089]
[58]
Tan SH, Nguyen NT, Chua YC, Kang TG. Oxygen plasma treatment for reducing hydrophobicity of a sealed polydimethylsiloxane microchannel. Biomicrofluidics 2010; 4(3): 32204.
[http://dx.doi.org/10.1063/1.3466882] [PMID: 21045926]
[59]
Abate AR, Krummel AT, Lee D, Marquez M, Holtze C, Weitz DA. Photoreactive coating for high-contrast spatial patterning of microfluidic device wettability. Lab Chip 2008; 8(12): 2157-60.
[http://dx.doi.org/10.1039/b813405g] [PMID: 19023480]
[60]
Yu H, Chong ZZ, Tor SB, Liu E, Loh NH. Low temperature and deformation-free bonding of PMMA microfluidic devices with stable hydrophilicity via oxygen plasma treatment and PVA coating. RSC Advances 2015; 5(11): 8377-88.
[http://dx.doi.org/10.1039/C4RA12771D]
[61]
Paar A. The SAXS guide: Anton Paar GmbH, Austria. 2011.
[62]
Mousa A, Kusminarto K. Suparta GB. A new simple method to measure the X-ray linear attenuation coefficients of materials using micro-digital radiography machine. Intl J Appl Eng Res 2017; 12(21): 10589-94.
[63]
Khvostichenko DS, Kondrashkina E, Perry SL, Pawate AS, Brister K, Kenis PJA. An X-ray transparent microfluidic platform for screening of the phase behavior of lipidic mesophases. Analyst 2013; 138(18): 5384-95.
[http://dx.doi.org/10.1039/c3an01174g] [PMID: 23882463]
[64]
Dhouib K, Khan Malek C, Pfleging W, et al. Microfluidic chips for the crystallization of biomacromolecules by counter-diffusion and on-chip crystal X-ray analysis. Lab Chip 2009; 9(10): 1412-21.
[http://dx.doi.org/10.1039/b819362b] [PMID: 19417908]
[65]
Gustafsson J, Ljusberg-Wahren H, Almgren M, Larsson K. Cubic lipid-water phase dispersed into submicron particles. Langmuir 1996; 12(20): 4611-3.
[http://dx.doi.org/10.1021/la960318y]
[66]
Spicer PT, Hayden KL, Lynch ML, Ofori-Boateng A, Burns JL. Novel process for producing cubic liquid crystalline nanoparticles (Cubosomes). Langmuir 2001; 17(19): 5748-56.
[http://dx.doi.org/10.1021/la010161w]
[67]
Wang W, Xie R, Ju XJ, et al. Controllable microfluidic production of multicomponent multiple emulsions. Lab Chip 2011; 11(9): 1587-92.
[http://dx.doi.org/10.1039/c1lc20065h] [PMID: 21461409]
[68]
Gu T, Yeap EW, Somasundar A, Chen R, Hatton TA, Khan SA. Droplet microfluidics with a nanoemulsion continuous phase. Lab Chip 2016; 16(14): 2694-700.
[http://dx.doi.org/10.1039/C6LC00601A] [PMID: 27306833]
[69]
Neves MA, Ribeiro HS, Kobayashi I, Nakajima M. Encapsulation of lipophilic bioactive molecules by microchannel emulsification. Food Biophys 2008; 3(2): 126-31.
[http://dx.doi.org/10.1007/s11483-008-9056-9]
[70]
Song H, Tice JD, Ismagilov RF. A microfluidic system for controlling reaction networks in time. Angew Chem 2003; 42(7): 768-72.
[http://dx.doi.org/10.1002/anie.200390203] [PMID: 12596195]
[71]
With S, Trebbin M, Bartz CB, et al. Fast diffusion-limited lyotropic phase transitions studied in situ using continuous flow microfluidics/microfocus-SAXS. Langmuir 2014; 30(42): 12494-502.
[http://dx.doi.org/10.1021/la502971m] [PMID: 25216394]
[72]
Kulkarni JA, Darjuan MM, Mercer JE, et al. On the formation and morphology of lipid nanoparticles containing ionizable cationic lipids and siRNA. ACS Nano 2018; 12(5): 4787-95.
[http://dx.doi.org/10.1021/acsnano.8b01516] [PMID: 29614232]
[73]
Ghazal A, Gontsarik M, Kutter JP, et al. Microfluidic platform for the continuous production and characterization of multilamellar vesicles: a synchrotron small-angle X-ray scattering (SAXS) study. J Phys Chem Lett 2017; 8(1): 73-9.
[http://dx.doi.org/10.1021/acs.jpclett.6b02468] [PMID: 27936765]
[74]
Chan JW, Winhold H, Lane SM. Optical trapping and coherent anti-Stokes Raman scattering (CARS) spectroscopy of submicron-size particles. IEEE J Sel Top Quantum Electron 2005; 11(4): 858-63.
[http://dx.doi.org/10.1109/JSTQE.2005.857381]
[75]
Kirchner SR, Ohlinger A, Pfeiffer T, et al. Membrane composition of jetted lipid vesicles: a Raman spectroscopy study. J Biophotonics 2012; 5(1): 40-6.
[http://dx.doi.org/10.1002/jbio.201100058] [PMID: 22147675]
[76]
Morikawa Y, Tagami T, Hoshikawa A, Ozeki T. The use of an efficient microfluidic mixing system for generating stabilized polymeric nanoparticles for controlled drug release. Biol Pharm Bull 2018; 41(6): 899-907.
[http://dx.doi.org/10.1248/bpb.b17-01036] [PMID: 29863078]
[77]
Lutz-Bueno V, Zhao J, Mezzenga R, Pfohl T, Fischer P, Liebi M. Scanning-SAXS of microfluidic flows: nanostructural mapping of soft matter. Lab Chip 2016; 16(20): 4028-35.
[http://dx.doi.org/10.1039/C6LC00690F] [PMID: 27713983]
[78]
Safinya CR, Sirota EB, Plano RJ. Nematic to smectic-A phase transition under shear flow: a nonequilibrium synchrotron X-ray study. Phys Rev Lett 1991; 66(15): 1986-9.
[http://dx.doi.org/10.1103/PhysRevLett.66.1986] [PMID: 10043361]
[79]
Balbino TA, Aoki NT, Gasperini AAM, et al. Continuous flow production of cationic liposomes at high lipid concentration in microfluidic devices for gene delivery applications. Chem Eng J 2013; 226: 423-33.
[http://dx.doi.org/10.1016/j.cej.2013.04.053]
[80]
Wi R, Oh Y, Chae C, Kim DH. Formation of liposome by microfluidic flow focusing and its application in gene delivery. Korea-Australia Rheol J 2012; 24(2): 129-35.
[http://dx.doi.org/10.1007/s13367-012-0015-0]
[81]
Valencia PM, Pridgen EM, Rhee M, Langer R, Farokhzad OC, Karnik R. Microfluidic platform for combinatorial synthesis and optimization of targeted nanoparticles for cancer therapy. ACS Nano 2013; 7(12): 10671-80.
[http://dx.doi.org/10.1021/nn403370e] [PMID: 24215426]
[82]
Liu K, Wang H, Chen KJ, et al. A digital microfluidic droplet generator produces self-assembled supramolecular nanoparticles for targeted cell imaging. Nanotechnology 2010; 21(44)445603
[http://dx.doi.org/10.1088/0957-4484/21/44/445603] [PMID: 20935351]
[83]
Chiesa E, Dorati R, Modena T, Conti B, Genta I. Multivariate analysis for the optimization of microfluidics-assisted nanoprecipitation method intended for the loading of small hydrophilic drugs into PLGA nanoparticles. Int J Pharm 2018; 536(1): 165-77.
[http://dx.doi.org/10.1016/j.ijpharm.2017.11.044] [PMID: 29175645]
[84]
Yadav SC, Kumari A, Yadav R. Development of peptide and protein nanotherapeutics by nanoencapsulation and nanobioconjugation. Peptides 2011; 32(1): 173-87.
[http://dx.doi.org/10.1016/j.peptides.2010.10.003] [PMID: 20934475]
[85]
Hermanson GT. Zero-length crosslinkers. In: Audet J, Preap M. Bioconjugate techniques. 3rd ed. Academic Press: Cambridge 2013; pp. 259-73.
[http://dx.doi.org/10.1016/B978-0-12-382239-0.00004-2]
[86]
Streck S, Clulow AJ, Nielsen HM, Rades T, Boyd BJ, McDowell A. The distribution of cell-penetrating peptides on polymeric nanoparticles prepared using microfluidics and elucidated with small angle X-ray scattering. J Colloid Interface Sci 2019; 555: 438-48.
[http://dx.doi.org/10.1016/j.jcis.2019.08.007] [PMID: 31400536]
[87]
Mieszawska AJ, Kim Y, Gianella A, et al. Synthesis of polymer-lipid nanoparticles for image-guided delivery of dual modality therapy. Bioconjug Chem 2013; 24(9): 1429-34.
[http://dx.doi.org/10.1021/bc400166j] [PMID: 23957728]
[88]
Guimarães Sá Correia M, Briuglia ML, Niosi F, Lamprou DA. Microfluidic manufacturing of phospholipid nanoparticles: stability, encapsulation efficacy, and drug release. Int J Pharm 2017; 516(1-2): 91-9.
[http://dx.doi.org/10.1016/j.ijpharm.2016.11.025] [PMID: 27840162]
[89]
Drummond DC, Meyer O, Hong K, Kirpotin DB, Papahadjopoulos D. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev 1999; 51(4): 691-743.
[PMID: 10581328]
[90]
Jager-Lezer N, Terrisse I, Bruneau F, et al. Influence of lipophilic surfactant on the release kinetics of water-soluble molecules entrapped in a W/O/W multiple emulsion. J Control Release 1997; 45(1): 1-13.
[http://dx.doi.org/10.1016/S0168-3659(96)01507-6]
[91]
Shimizu M, Nakane Y. Encapsulation of biologically active proteins in a multiple emulsion. Biosci Biotechnol Biochem 1995; 59(3): 492-6.
[http://dx.doi.org/10.1271/bbb.59.492] [PMID: 7537555]
[92]
Salim M, Khan J, Ramirez G, et al. Interactions of artefenomel (OZ439) with milk during digestion: insights into digestion-driven solubilization and polymorphic transformations. Mol Pharm 2018; 15(8): 3535-44.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00541] [PMID: 29932660]
[93]
Khalid N, Kobayashi I, Neves MA, Uemura K, Nakajima M, Nabetani H. Microchannel emulsification study on formulation and stability characterization of monodisperse oil-in-water emulsions encapsulating quercetin. Food Chem 2016; 212: 27-34.
[http://dx.doi.org/10.1016/j.foodchem.2016.05.154] [PMID: 27374502]
[94]
Krzysztoń R, Salem B, Lee DJ, Schwake G, Wagner E, Rädler JO. Microfluidic self-assembly of folate-targeted monomolecular siRNA-lipid nanoparticles. Nanoscale 2017; 9(22): 7442-53.
[http://dx.doi.org/10.1039/C7NR01593C] [PMID: 28530287]
[95]
Dolomite Microfluidics. Available at:. https://www. dolomite-microfluidics.com/


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 7
ISSUE: 6
Year: 2019
Page: [423 - 443]
Pages: 21
DOI: 10.2174/2211738507666191019154815

Article Metrics

PDF: 47
HTML: 9