Abstract
A wide range of studies have shown that liposomes can act as suitable adjuvants for a range of vaccine antigens. Properties such as their amphiphilic character and biphasic nature allow them to incorporate antigens within the lipid bilayer, on the surface, or encapsulated within the inner core. However, appropriate methods for the manufacture of liposomes are limited and this has resulted in issues with cost, supply, and wider scale application of these systems. Within this chapter we explore manufacturing processes that can be used for the production of liposomal adjuvants, and we outline new manufacturing methods can that offer fast, scalable, and cost-effective production of liposomal adjuvants.
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Leroux-Roels G (2010) Unmet needs in modern vaccinology: adjuvants to improve the immune response. Vaccine 28(Suppl 3): C25–C36
Nordly P et al (2009) Status and future prospects of lipid-based particulate delivery systems as vaccine adjuvants and their combination with immunostimulators. Expert Opin Drug Deliv 6(7):657–672
Foged C (2011) Subunit vaccines of the future: the need for safe, customized and optimized particulate delivery systems. Ther Deliv 2(8):1057–1077
Allison AC, Gregoriadis G (1974) Liposomes as immunological adjuvants. Nature 252:252
Korsholm KS et al (2007) The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes. Immunology 121(2):216–226
Henriksen-Lacey M, Devitt A, Perrie Y (2011) The vesicle size of DDA:TDB liposomal adjuvants plays a role in the cell-mediated immune response but has no significant effect on antibody production. J Control Release 154(2): 131–137
Henriksen-Lacey M et al (2010) Liposomal cationic charge and antigen adsorption are important properties for the efficient deposition of antigen at the injection site and ability of the vaccine to induce a CMI response. J Control Release 145(2):102–108
Christensen D et al (2012) A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog. J Control Release 160(3):468–476
Zahringer U et al (2008) TLR2—promiscuous or specific? A critical re-evaluation of a receptor expressing apparent broad specificity. Immunobiology 213(3-4):205–224
Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4(2):145–160
Perrie Y et al (2013) A case-study investigating the physicochemical characteristics that dictate the function of a liposomal adjuvant. Hum Vaccin Immunother 9(6):1374–1381
Aguilar JC, Rodriguez EG (2007) Vaccine adjuvants revisited. Vaccine 25(19):3752–3762
Brewer JM et al (2004) Vesicle size influences the trafficking, processing, and presentation of antigens in lipid vesicles. J Immunol 173(10):6143–6150
Dua JS, Rana AC, Bhandari AK (2012) Liposome: methods of preparation and applications. Int J Pharm Stud Res 3(2):14–20
Bangham A, Standish M, Watkins J (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13(1):238–252
Gregoriadis G et al (2002) A role for liposomes in genetic vaccination. Vaccine 20:B1–B9
Wagner A, Vorauer-Uhl K (2011) Liposome Technology for Industrial Purposes. J Drug Deliv 2011, 591325. doi:10.1155/2011/591325
Szoka F Jr, Papahadjopoulos D (1980) Comparative properties and methods of preparation of lipid vesicles (liposomes). Annu Rev Biophys Bioeng 9(1):467–508
Papahadjopoulos D, Miller N (1967) Phospholipid model membranes. I. Structural characteristics of hydrated liquid crystals. Biochim Biophys Acta 135(4):624–638
Papahadjopoulos D, Watkins JC (1967) Phospholipid model membranes. II. Permeability properties of hydrated liquid crystals. Biochim Biophys Acta 135(4):639–652
Uchegbu IF et al (2013) Fundamentals of pharmaceutical nanoscience. Springer, New York
Lapinski MM et al (2007) Comparison of liposomes formed by sonication and extrusion: rotational and translational diffusion of an embedded chromophore. Langmuir 23(23):11677–11683
Foged C et al (2014) Subunit vaccine delivery. Springer, New York
Liu R (2008) Water-insoluble drug formulation, 2nd edn. CRC Press, Boca Raton, FL
Richardson ES, Pitt WG, Woodbury DJ (2007) The role of cavitation in liposome formation. Biophys J 93(12):4100–4107
Riaz M (1996) Liposomes preparation methods. Pak J Pharm Sci 9(1):65–77
Kataria S et al (2011) Stealth liposomes: a review. Int J Res Ayurveda Pharm 2(5):1534–1538
Lasic DD (1988) The mechanism of vesicle formation. Biochem J 256(1):1
Andreasen LV, Wood G, Christensen D (2012) Methods for producing liposomes. Google Patents
Brandl M et al (1990) Liposome preparation by a new high pressure homogenizer Gaulin Micron Lab 40. Drug Dev Ind Pharm 16(14):2167–2191
Barnadas-Rodrı́guez R, Sabés M (2001) Factors involved in the production of liposomes with a high-pressure homogenizer. Int J Pharm 213(1):175–186
Olson F et al (1979) Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes. Biochim Biophys Acta 557(1):9–23
Bergstrand N et al (2003) Interactions between pH-sensitive liposomes and model membranes. Biophys Chem 104(1):361–379
Batzri S, Korn ED (1973) Single bilayer liposomes prepared without sonication. Biochim Biophys Acta 298(4):1015–1019
Jaafar-Maalej C et al (2010) Ethanol injection method for hydrophilic and lipophilic drug-loaded liposome preparation. J Liposome Res 20(3):228–243
Hauschild S et al (2005) Direct preparation and loading of lipid and polymer vesicles using inkjets. Small 1(12):1177–1180
Bogy D, Talke FE (1984) Experimental and theoretical study of wave propagation phenomena in drop-on-demand ink jet devices. IBM J Res Dev 28(3):314–321
Frederiksen L et al (1997) Preparation of liposomes encapsulating water‐soluble compounds using supercritical carbon dioxide. J Pharm Sci 86(8):921–928
Song Y, Hormes J, Kumar CS (2008) Microfluidic synthesis of nanomaterials. Small 4(6):698–711
Demello AJ (2006) Control and detection of chemical reactions in microfluidic systems. Nature 442(7101):394–402
Nguyen N-T, Wu Z (2005) Micromixers—a review. J Micromech Microeng 15(2):R1
Squires TM, Quake SR (2005) Microfluidics: fluid physics at the nanoliter scale. Rev Mod Phys 77(3):977
Capretto L et al (2011) Micromixing within microfluidic devices. Top Curr Chem 304:27–68
Chang H-I, Yeh M-K (2012) Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy. Int J Nanomedicine 7:49
Weigl BH, Bardell RL, Cabrera CR (2003) Lab-on-a-chip for drug development. Adv Drug Deliv Rev 55(3):349–377
Whitesides GM (2006) The origins and the future of microfluidics. Nature 442(7101):368–373
Dittrich PS, Manz A (2006) Lab-on-a-chip: microfluidics in drug discovery. Nat Rev Drug Discov 5(3):210–218
Hood R, Vreeland W, DeVoe D (2014) Microfluidic remote loading for rapid single-step liposomal drug preparation. Lab Chip 14(17):3359–3367
van Swaay D (2013) Microfluidic methods for forming liposomes. Lab Chip 13(5):752–767
Weibel DB, Whitesides GM (2006) Applications of microfluidics in chemical biology. Curr Opin Chem Biol 10(6):584–591
Jensen KF (2001) Microreaction engineering—is small better? Chem Eng Sci 56(2):293–303
Stroock AD et al (2002) Chaotic mixer for microchannels. Science 295(5555):647–651
Stainmesse S et al (1995) Formation and stabilization of a biodegradable polymeric colloidal suspension of nanoparticles. Colloid Polymer Sci 273(5):505–511
Mora-Huertas C, Fessi H, Elaissari A (2011) Influence of process and formulation parameters on the formation of submicron particles by solvent displacement and emulsification–diffusion methods: critical comparison. Adv Colloid Interface Sci 163(2):90–122
RemziáBecer C (2009) Synthetic polymeric nanoparticles by nanoprecipitation. J Mater Chem 19(23):3838–3840
Govender T et al (1999) PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. J Control Release 57(2):171–185
Lee C-Y et al (2011) Microfluidic mixing: a review. Int J Mol Sci 12(5):3263–3287
Mengeaud V, Josserand J, Girault HH (2002) Mixing processes in a zigzag microchannel: finite element simulations and optical study. Anal Chem 74(16):4279–4286
Jahn A et al (2007) Microfluidic directed formation of liposomes of controlled size. Langmuir 23(11):6289–6293
Valencia PM et al (2010) Single-step assembly of homogenous lipid−polymeric and lipid−quantum dot nanoparticles enabled by microfluidic rapid mixing. ACS Nano 4(3):1671–1679
Bally F et al (2012) Improved size-tunable preparation of polymeric nanoparticles by microfluidic nanoprecipitation. Polymer 53(22):5045–5051
Zhigaltsev IV et al (2012) Bottom-up design and synthesis of limit size lipid nanoparticle systems with aqueous and triglyceride cores using millisecond microfluidic mixing. Langmuir 28(7):3633–3640
Belliveau NM et al (2012) Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Mol Ther Nucleic Acids 1(8), e37
Kastner E et al (2014) High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization. Int J Pharm 477(1-2):361–368
Kastner E et al (2015) Microfluidic-controlled manufacture of liposomes for the solubilisation of a poorly water soluble drug. Int J Pharm 485(1):122–130
Yu B, Lee RJ, Lee LJ (2009) Microfluidic methods for production of liposomes. Methods Enzymol 465:129–141
Schwendener RA (2014) Liposomes as vaccine delivery systems: a review of the recent advances. Ther Adv Vaccines 2(6):159–182
Gobby D, Angeli P, Gavriilidis A (2001) Mixing characteristics of T-type microfluidic mixers. J Micromech Microeng 11(2):126
Erbacher C et al (1999) Towards integrated continuous-flow chemical reactors. Microchim Acta 131(1-2):19–24
Lee JN, Park C, Whitesides GM (2003) Solvent compatibility of poly (dimethylsiloxane)-based microfluidic devices. Anal Chem 75(23):6544–6554
Wu Z, Nguyen N-T (2005) Rapid mixing using two-phase hydraulic focusing in microchannels. Biomed Microdevices 7(1):13–20
Quevedo E, Steinbacher J, McQuade DT (2005) Interfacial polymerization within a simplified microfluidic device: capturing capsules. J Am Chem Soc 127(30):10498–10499
Acknowledgements
This work was part funded by EU Horizon 2020 project TBVAC 2020 (Grant no. 643381) (Y.P. & C.B.R.), the EPSRC Centre for Innovative Manufacturing in Emergent Macromolecular Therapies (E.K.), Aston University (S.K.), and the EPSRC iCASE Scheme (Grant no. BB/L017245/1) (P.S.).
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Perrie, Y., Kastner, E., Khadke, S., Roces, C.B., Stone, P. (2017). Manufacturing Methods for Liposome Adjuvants. In: Fox, C. (eds) Vaccine Adjuvants. Methods in Molecular Biology, vol 1494. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6445-1_9
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DOI: https://doi.org/10.1007/978-1-4939-6445-1_9
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