Abstract
Vesicles are compartments enclosed by a thin membrane, which is made up of amphiphilic molecules arranged into ordered layers. Vesicle-like structures are Nature’s choice for encapsulating important biochemical species that enable living processes, and are increasingly important as artificial structures for the encapsulation and release of drugs, biomolecules and other active ingredients for biomedical, pharmaceutical, food and consumer industries. Advances in microfluidic technologies have provided a new set of tools for unraveling the science behind formation of vesicles and fabricating novel vesicles. While traditional approaches for fabricating vesicles rely on self-assembly of amphiphiles, the precise control of flow afforded in microfluidic devices enables directed assembly of the amphiphiles. Thus, techniques such as hydrodynamic flow focusing, controlled emulsion-templating and pulsatile jetting offer unprecedented degree of control over vesicle structures. This creates new opportunities to engineer the structures of vesicles and tailor them for specific applications. In this review, we introduce current understanding behind different kinds of vesicles, survey conventional and microfluidic techniques for their formation, discuss new approaches of encapsulation and release of active ingredients in microfluidic vesicles, and point to future research and development in the area.
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References
New, R.R.C.: Liposomes : A Practical Approach. IRL Press, Oxford (1990). (Oxford University Press)
Discher, B.M., et al.: Polymersomes: Tough vesicles made from diblock copolymers. Science 284, 1143–1146 (1999)
Zhang, L., Eisenberg, A.: Multiple morphologies of “Crew-Cut” aggregates of polystyrene-b-poly(acrylic acid) block copolymers. Science 268, 1728–1731 (1995)
Munoz, S., et al.: Ultrathin monolayer lipid-membranes from a new family of crown ether-based bolar-amphiphiles. J. Am. Chem. Soc. 115, 1705–1711 (1993)
Schreier, H., Bouwstra, J.: Liposomes and niosomes as topical drug carriers—dermal and transdermal drug-delivery. J. Control. Release 30, 1–15 (1994)
Dinsmore, A.D., et al.: Colloidosomes: selectively permeable capsules composed of colloidal particles. Science 298, 1006–1009 (2002)
Hsu, M.F., et al.: Self-assembled shells composed of colloidal particles: fabrication and characterization. Langmuir 21, 2963–2970 (2005)
Segota, S., Tezak, D.: Spontaneous formation of vesicles. Adv. Colloid Interface Sci. 121, 51–75 (2006)
Antonietti, M., Förster, S.: Vesicles and liposomes: a self-assembly principle beyond lipids. Adv. Mater. 15, 1323–1333 (2003)
Lasic, D.D.: The mechanism of vesicle formation. Biochem. J. 256, 1–11 (1988)
Kita-Tokarczyk, K., et al.: Block copolymer vesicles—using concepts from polymer chemistry to mimic biomembranes. Polymer 46, 3540–3563 (2005)
Wang, Z.G.: Curvature instability of diblock copolymer bilayers. Macromolecules 25, 3702–3705 (1992)
Marrink, S.J., Mark, A.E.: Molecular dynamics simulation of the formation, structure, and dynamics of small phospholipid vesicles. J. Am. Chem. Soc. 125, 15233–15242 (2003)
Uneyama, T.: Density functional simulation of spontaneous formation of vesicle in block copolymer solutions. J. Chem. Phys. 126, 114902 (2007)
Yamamoto, S., et al.: Dissipative particle dynamics study of spontaneous vesicle formation of amphiphilic molecules. J. Chem. Phys. 116, 5842–5849 (2002)
Noguchi, H., Takasu, M.: Self-assembly of amphiphiles into vesicles: a Brownian dynamics simulation. Phys. Rev. E 64, 041913 (2001)
Du, J., O’Reilly, R.K.: Advances and challenges in smart and functional polymer vesicles. Soft Matter 5, 3544–3561 (2009)
He, X.H., Schmid, F.: Dynamics of spontaneous vesicle formation in dilute solutions of amphiphilic diblock copolymers. Macromolecules 39, 2654–2662 (2006)
Rank, A., et al.: Preparation of monodisperse block copolymer vesicles via a thermotropic cylinder-vesicle transition. Langmuir 25, 1337–1344 (2009)
Discher, D.E., Ahmed, F.: Polymersomes. Ann. Rev. Biomed. Eng. 8, 323–341 (2006)
Israelachvili, J.N., et al.: Theory of self-assembly of hydrocarbon amphiphiles into micelles and bilayers. J. Chem. Soc. Faraday Trans. Ii 72, 1525–1568 (1976)
Won, Y.Y., et al.: Cryogenic transmission electron microscopy (cryo-TEM) of micelles and vesicles formed in water by polyethylene oxide)-based block copolymers. J. Phys. Chem. B 106, 3354–3364 (2002)
Hyde, S.T.: Curvature and the global structure of interfaces in surfactant-water systems. J. De Phys. 51, C7209–C7228 (1990)
Bates, F.S., Fredrickson, G.H.: Block copolymer thermodynamics—theory and experiment. Ann. Rev. Phys. Chem. 41, 525–557 (1990)
Bates, F.S.: Polymer–polymer phase-behavior. Science 251, 898–905 (1991)
Bermudez, H., et al.: Molecular weight dependence of polymersome membrane structure, elasticity, and stability. Macromolecules 35, 8203–8208 (2002)
Dobereiner, H.G., et al.: Mapping vesicle shapes into the phase diagram: a comparison of experiment and theory. Phys. Rev. E 55, 4458–4474 (1997)
Mui, B.L.S., et al.: Influence of transbilayer area asymmetry on the morphology of large unilamellar vesicles. Biophys. J. 69, 930–941 (1995)
Storm, G., Crommelin, D.J.A.: Liposomes: quo vadis? Pharm. Sci. Technol. Today 1, 19–31 (1998)
Angelova, M.I., Dimitrov, D.S.: Liposome electroformation. Faraday Discuss. Chem. Soc. 81, 303–311 (1986)
Sun, B.Y., Chiu, D.T.: Determination of the encapsulation efficiency of individual vesicles using single-vesicle photolysis and confocal single-molecule detection. Anal. Chem. 77, 2770–2776 (2005)
Howse, J.R., et al.: Templated formation of giant polymer vesicles with controlled size distributions. Nat. Mater. 8, 507–511 (2009)
Taylor, P., et al.: Fabrication of 2D arrays of giant liposomes on solid substrates by microcontact printing. Phys. Chem. Chem. Phys. 5, 4918–4922 (2003)
Evans, E., Needham, D.: Physical properties of surfactant bilayer membranes: thermal transitions, elasticity, rigidity, cohesion and colloidal interactions. J. Phys. Chem. 91, 4219–4228 (1987)
Mui, B., et al.: Extrusion technique to generate liposomes of defined size. Liposomes Pt A 367, 3–14 (2003)
Macdonald, R.C., et al.: Small-volume extrusion apparatus for preparation of large, unilamellar vesicles. Biochim. Biophys. Acta 1061, 297–303 (1991)
Frisken, B.J., et al.: Studies of vesicle extrusion. Langmuir 16, 928–933 (2000)
Pautot, S., et al.: Production of unilamellar vesicles using an inverted emulsion. Langmuir 19, 2870–2879 (2003)
Pautot, S., et al.: Engineering asymmetric vesicles. Proc. Natl. Acad. Sci. USA 100, 10718–10721 (2003)
Shah, R.K., et al.: Designer emulsions using microfluidics. Mater. Today 11, 18–27 (2008)
Squires, T.M., Quake, S.R.: Microfluidics: fluid physics at the nanoliter scale. Rev. Mod. Phys. 77, 977–1026 (2005)
Brody, J.P., et al.: Biotechnology at low Reynolds numbers. Biophys. J. 71, 3430–3441 (1996)
Knight, J.B., et al.: Hydrodynamic focusing on a silicon chip: mixing nanoliters in microseconds. Phys. Rev. Lett. 80, 3863–3866 (1998)
Beebe, D.J., et al.: Physics and applications of microfluidics in biology. Ann. Rev. Biomed. Eng. 4, 261–286 (2002)
Gambin, Y., et al.: Ultrafast microfluidic mixer with three-dimensional flow focusing for studies of biochemical kinetics. Lab Chip 10, 598–609 (2010)
Pollack, L., et al.: Compactness of the denatured state of a fast-folding protein measured by submillisecond small-angle x-ray scattering. Proc. Natl. Acad. Sci. USA 96, 10115–10117 (1999)
Lipman, E.A., et al.: Single-molecule measurement of protein folding kinetics. Science 301, 1233–1235 (2003)
Koester, S., et al.: Visualization of flow-aligned type I collagen self-assembly in tunable pH gradients. Langmuir 23, 357–359 (2007)
Koester, S., et al.: An in situ study of collagen self-assembly processes. Biomacromolecules 9, 199–207 (2008)
Yun, J., et al.: Continuous production of solid lipid nanoparticles by liquid flow-focusing and gas displacing method in microchannels. Chem. Eng. Sci. 64, 4115–4122 (2009)
Jahn, A., et al.: Microfluidic mixing and the formation of nanoscale lipid vesicles. ACS Nano 4, 2077–2087 (2010)
Jahn, A., et al.: Controlled vesicle self-assembly in microfluidic channels with hydrodynamic focusing. J. Am. Chem. Soc. 126, 2674–2675 (2004)
Jahn, A., et al.: Microfluidic directed formation of liposomes of controlled size. Langmuir 23, 6289–6293 (2007)
Massignani, M., et al.: Controlling cellular uptake by surface chemistry, size, and surface topology at the nanoscale. Small 5, 2424–2432 (2009)
Gullotti, E., Yeo, Y.: Extracellularly activated nanocarriers: a new paradigm of tumor targeted drug delivery. Mol. Pharm. 6, 1041–1051 (2009)
Hong, J.S., et al.: Microfluidic directed self-assembly of liposome-hydrogel hybrid nanoparticles. Langmuir 26, 11581–11588 (2010)
Seiffert, S., et al.: Smart microgel capsules from macromolecular precursors. J. Am. Chem. Soc. 132, 6606–6609 (2010)
Thiele, J., et al.: Preparation of monodisperse block copolymer vesicles via flow focusing in microfluidics. Langmuir 26, 6860–6863 (2010)
Brown, L., et al.: Polymersome production on a microfluidic platform using pH sensitive block copolymers. Lab Chip 10, 1922–1928 (2010)
Karnik, R., et al.: Microfluidic platform for controlled synthesis of polymeric nanoparticles. Nano Lett. 8, 2906–2912 (2008)
Kolishetti, N. et al.: Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy. Proceedings of the National Academy of Sciences of the United States of America, vol. 107, pp. 17939–17944. 19 Oct 2010 (2010)
Tan, Y.C., et al.: Controlled microfluidic encapsulation of cells, proteins, and microbeads in lipid vesicles. J. Am. Chem. Soc. 128, 5656–5658 (2006)
Shum, H.C., et al.: Microfluidic fabrication of monodisperse biocompatible and biodegradable polymersomes with controlled permeability. J. Am. Chem. Soc. 130, 9543–9549 (2008)
Shum, H.C., et al.: Double emulsion templated monodisperse phospholipid vesicles. Langmuir 24, 7651–7653 (2008)
Hayward, R.C., et al.: Dewetting Instability during the Formation of polymersomes from block-copolymer-stabilized double emulsions. Langmuir 22, 4457–4461 (2006)
Shum, H.C., et al.: Dewetting-induced membrane formation by adhesion of amphiphile-laden interfaces. J. Am. Chem. Soc. 133, 4420–4426 (2011)
Funakoshi, K., et al.: Formation of giant lipid vesiclelike compartments from a planar lipid membrane by a pulsed jet flow. J. Am. Chem. Soc. 129, 12608 (2007)
Stachowiak, J.C., et al.: Unilamellar vesicle formation and encapsulation by microfluidic jetting. Proc. Natl. Acad. Sci. USA 105, 4697–4702 (2008)
Ota, S., et al.: Microfluidic formation of monodisperse, cell-sized, and unilamellar vesicles. Angew. Chem. Int. Ed. 48, 6533–6537 (2009)
Beales, P.A., et al.: Specific adhesion between DNA-functionalized “Janus’’ vesicles: size-limited clusters. Soft Matter 7, 1747–1755 (2011)
Shum, H.C., et al.: Multicompartment polymersomes from double emulsions. Angew. Chem. Int. Ed. 50, 1648–1651 (2011)
Kisak, E.T., et al.: The vesosome—A multicompartment drug delivery vehicle. Curr. Med. Chem. 11, 199–219 (2004)
Kim, S.H., et al.: Multiple polymersomes for programmed release of multiple components. J. Am. Chem. Soc. 133, 15165–15171 (2011). doi:10.1021/ja205687k
Onaca, O., et al.: Stimuli-responsive polymersomes as nanocarriers for drug and gene delivery. Macromol. Biosci. 9, 129–139 (2009)
Brochard-Wyart, F., et al.: Transient pores in stretched vesicles: role of leak-out. Physica A 278, 32–51 (2000)
Karatekin, E., et al.: Transient pores in vesicles. Polym. Int. 52, 486–493 (2003)
Karatekin, E., et al.: Cascades of transient pores in giant vesicles: line tension and transport. Biophys. J. 84, 1734–1749 (2003)
Sandre, O., et al.: Dynamics of transient pores in stretched vesicles. Proc. Natl. Acad. Sci. 96, 10591 (1999)
Ahmed, F., Discher, D.E.: Self-porating polymersomes of PEG-PLA and PEG-PCL: hydrolysis-triggered controlled release vesicles. J. Controlled Release 96, 37–53 (2004)
Zhang, Z., et al.: The in vivo and in vitro degradation behavior of poly(trimethylene carbonate). Biomaterials 27, 1741–1748 (2006)
Sanson, C., et al.: Biocompatible and Biodegradable Poly(trimethylene carbonate)-b-Poly (l-glutamic acid) Polymersomes: size control and stability. Langmuir 26, 2751–2760 (2010)
Gallagher, F.A., et al.: Magnetic resonance imaging of pH in vivo using hyperpolarized C-13-labelled bicarbonate. Nature 453, 940–973 (2008)
Gerweck, L.E., Seetharaman, K.: Cellular pH gradient in tumor versus normal tissue: Potential exploitation for the treatment of cancer. Cancer Res. 56, 1194–1198 (1996)
Chen, W., et al.: pH-Sensitive degradable polymersomes for triggered release of anticancer drugs: A comparative study with micelles. J. Controlled Release 142, 40–46 (2010)
Agut, W., et al.: pH and temperature responsive polymeric micelles and polymersomes by self-assembly of Poly 2-(dimethylamino)ethyl methacrylate -b-Poly(glutamic acid) double hydrophilic block copolymers. Langmuir 26, 10546–10554 (2010)
Needham, D., Dewhirst, M.W.: The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors. Adv. Drug Deliv. Rev. 53, 285–305 (2001)
Hong, C.Y., et al.: Synthesis and characterization of well-defined diblock and triblock copolymers of poly(N-isopropylacrylamide) and poly(ethylene oxide). J. Polym. Sci. Part A-Polym. Chem. 42, 4873–4881 (2004)
Qin, S., et al.: Temperature-controlled assembly and release from polymer vesicles of poly(ethylene oxide)-block-poly(N-isopropylacrylamide). Adv. Mater. 18, 2905 (2006)
Napoli, A., et al.: Glucose-oxidase based self-destructing polymeric vesicles. Langmuir 20, 3487–3491 (2004)
Cerritelli, S., et al.: PEG-SS-PPS: reduction-sensitive disulfide block copolymer vesicles for intracellular drug delivery. Biomacromolecules 8, 1966–1972 (2007)
Kuai, R., et al.: Efficient delivery of payload into tumor cells in a controlled manner by TAT and thiolytic cleavable PEG Co-modified liposomes. Mol. Pharm. 7, 1816–1826 (2010)
Song, L., et al.: Structure of staphylococcal α-Hemolysin, a heptameric transmembrane pore. Science 274, 1859–1865 (1996)
Nisisako, T., Torii, T.: Microfluidic large-scale integration on a chip for mass production of monodisperse droplets and particles. Lab Chip 8, 287–293 (2008)
Malloggi, F., et al.: Monodisperse colloids synthesized with nanofluidic technology. Langmuir 26, 2369–2373 (2010)
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Shum, H.C., Thiele, J., Kim, SH. (2014). Microfluidic Fabrication of Vesicles. In: Wang, L. (eds) Advances in Transport Phenomena 2011. Advances in Transport Phenomena, vol 3. Springer, Cham. https://doi.org/10.1007/978-3-319-01793-8_1
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