Skip to main content
SpringerLink
Log in

Formulation and Characterisation of PLGA Microspheres as Vaccine Adjuvants

  • Chapter
  • First Online:
Immunomic Discovery of Adjuvants and Candidate Subunit Vaccines

Part of the book series: Immunomics Reviews: ((IMMUN,volume 5))

Abstract

There appear to be several factors that confirm the viability of polymeric microspheres as vaccine delivery vehicles, including the ability to enhance targeting of antigen-presenting cells, the potential for controlled, sustained release of antigen-thereby potentially eliminating the need for multiple vaccination doses-as well as the ability of the polymer matrix to not only facilitate more efficient delivery by acting as a shield from the hostile external environment, but also the potential to reduce adverse reactions and abrogate problems caused by the vaccine strain in immunocompromised individuals. In addition, microspheres offer great variability in terms of manufacturing processes, constituents (including additional adjuvants), physico-chemical properties and immunological efficacy.

This chapter investigates the advantageous properties of microspheres—and more specifically, those composed primarily of polylactide-co-glycolide—for the delivery of vaccine adjuvants by outlining the various preparation techniques and the effect of the related processing parameters, the subsequent in vivo efficacy, and, finally, the potential for a desirable product with an extended shelf-life.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Agger E, Andersen P (2001) Tuberculosis subunit vaccine development: on the role of interferon-gamma. Vaccine 19:2298–2302

    Article  PubMed  CAS  Google Scholar 

  2. Aldous B, Auffret A, Franks F (1995) The crystallisation of hydrates from amorphous carbohydrates. Cryo Letters 16:181–186

    CAS  Google Scholar 

  3. Allemann E, Gurny R, Doelker E (1992) Preparation of aqueous polymeric nanodispersions by a reversible salting-out process: influence of process parameters on particle size. Int J Pharm 87:247–253

    Article  CAS  Google Scholar 

  4. Allison A, Gregoriadis G (1974) Liposomes as immunological adjuvants. Nature 252:252

    Article  PubMed  CAS  Google Scholar 

  5. Allison S, Molina M, Anchordoquy T (2000) Stabilisation of lipid DNA complexes during the freezing step of the lyophilization process: the particle isolation hypothesis. Biochim Biophys Acta 1468:127–138

    Article  PubMed  CAS  Google Scholar 

  6. Anchordoquy T, Allison S, Molina M, Girouard L, Carson T (2001) Physical stabilization of DNA-based therapeutics. Drug Discov Today 6:463–470

    Article  PubMed  CAS  Google Scholar 

  7. Arshady R (1991) Preparation of biodegradable microspheres and microcapsules: 2. Polyactides and related polyesters. J Control Release 17:1–21

    Article  CAS  Google Scholar 

  8. Audran R, Peter K, Dannull J, Men Y, Scandella E, Groettrup M, Gander B, Corradin G (2003) Encapsulation of peptides in biodegradable microspheres prolongs their MHC class-I presentation by dendritic cells and macrophages in vitro. Vaccine 21:1250–1255

    Article  PubMed  CAS  Google Scholar 

  9. Bendix D (1998) Chemical synthesis of polylactide and its copolymers for medical applications. Polym Degrad Stabil 59:125–135

    Article  Google Scholar 

  10. Benoit M, Baras B, Gillard J (1999) Preparation and characterization of protein-loaded poly(epsilon-caprolactone) microparticles for oral vaccine delivery. Int J Pharm 184:73–84

    Article  PubMed  CAS  Google Scholar 

  11. Boury F, Ivanova T, Panaiotov I, Proust J, Bois A, Richou J (1995) Dynamic properties of poly(DL-lactide) and polyvinyl alcohol monolayers at the air/water and dichloromethane/water interfaces. J Colloid Interface Sci 169:380–392

    Article  CAS  Google Scholar 

  12. Bozdag S, Dillen K, Vandervoort J, Ludwig A (2005) The effect of freeze-drying with different cryoprotectants and gamma-irradiation sterilization on the characteristics of ciprofloxacin HCl-loaded poly(D, L-lactide-glycolide) nanoparticles. J Pharm Pharmacol 57:699–707

    Article  PubMed  CAS  Google Scholar 

  13. Bramwell V, Perrie Y (2005) Particulate delivery systems for vaccines. Crit Rev Ther Drug Carrier Syst 22:151–214

    Article  PubMed  CAS  Google Scholar 

  14. Briones M, Singh M, Ugozzoli M, Kazzaz J, Klakamp S, Ott G, O’Hagan D (2001) The preparation, characterization, and evaluation of cationic microparticles for DNA vaccine delivery. Pharm Res 18:709–712

    Article  PubMed  CAS  Google Scholar 

  15. Brunner R, Wallmann J, Szalai K, Karagiannis P, Kopp T, Scheiner O, Jensen-Jarolim E, Pali-Scholl I (2007) The impact of aluminium in acid-suppressing drugs on the immune response of BALB/c mice. Clin Exp Allergy 37:1566–1573

    Article  PubMed  CAS  Google Scholar 

  16. Burns RJ, Vitale K, Sanders L (1990) Nafarelin controlled release injectable: theoretical clinical plasma profiles from multiple dosing and from mixtures of microspheres containing 2 per cent, 4 per cent and 7 per cent nafarelin. J Microencapsul 7:397–413

    Article  PubMed  CAS  Google Scholar 

  17. Capan Y, Woo B, Gebrekidan S, Ahmed S, DeLuca P (1999) Influence of formulation parameters on the characteristics of poly(D, L-lactide-co-glycolide) microspheres containing poly(L-lysine) complexed plasmid DNA. J Control Release 60:279–286

    Article  PubMed  CAS  Google Scholar 

  18. Carmona-Ribeiro A, Ortis F, Schumacher R, Armelin M (1997) Interactions between cationic vesicles and cultured mammalian cells. Langmuir 13:2215–2218

    Article  CAS  Google Scholar 

  19. Chacon M, Molpeceres J, Berges L, Guzman M, Aberturas M (1999) Stability and freeze-drying of cyclosporine loaded poly(D, L lactide-glycolide) carriers. Eur J Pharm Sci 8:99–107

    Article  PubMed  CAS  Google Scholar 

  20. Choi S, Kwon H, Kim W, Kim J (2002) Thermodynamic parameters on poly(d, l-lactide-co-glycolide) particle size in emulsification-diffusion process. Colloids Surf A Physicochem Eng Asp 201:283–289

    Article  CAS  Google Scholar 

  21. Chong C, Cao M, Wong W, Fischer K, Addison W, Kwon G, Tyrrell D, Samuel J (2005) Enhancement of T helper type 1 immune responses against hepatitis B virus core antigen by PLGA nanoparticle vaccine delivery. J Control Release 102:85–99

    Article  PubMed  CAS  Google Scholar 

  22. Christensen D, Foged C, Rosenkrands I, Nielsen H, Andersen P, Agger E (2007) Trehalose preserves DDA/TDB liposomes and their adjuvant effect during freeze-drying. Biochim Biophys Acta 1768:2120–2129

    Article  PubMed  CAS  Google Scholar 

  23. Chung T, Wu S, Yao M, Lu C, Lin Y, Hung Y, Mou C, Chen Y, Huang D (2007) The effect of surface charge on the uptake and biological function of mesoporous silica nanoparticles in 3T3-L1 cells and human mesenchymal stem cells. Biomaterials 28:2959–2966

    Article  PubMed  CAS  Google Scholar 

  24. Cohen S, Chen L, Apte R (1995) Controlled release of peptides and proteins from biodegradable polyester microspheres: an approach for treating infectious diseases and malignancies. React Polym 25:177–187

    Article  CAS  Google Scholar 

  25. Conway A, Madrigal-Estebas L, McClean S, Brayden D, Mills K (2001) Protection against Bordetella pertussis infection following parenteral or oral immunization with antigens entrapped in biodegradable particles: effect of formulation and route of immunization on induction of Th1 and Th2 cells. Vaccine 19:1940–1950

    Article  PubMed  CAS  Google Scholar 

  26. Cooper A, Dalton D, Stewart T, Griffin J, Russell D, Orme I (1993) Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med 178:2243–2247

    Article  PubMed  CAS  Google Scholar 

  27. Copland M, Rades T, Davies N (2000) Hydration of lipid films with an aqueous solution of Quil A: a simple method for the preparation of immune-stimulating complexes. Int J Pharm 196:135–139

    Article  PubMed  CAS  Google Scholar 

  28. Crowe J, Crowe L (1988) Factors affecting the stability of dry liposomes. Biochim Biophys Acta 939:327–334

    Article  PubMed  CAS  Google Scholar 

  29. Crowe L, Reid D, Crowe J (1996) Is trehalose special for preserving dry biomaterials? Biophys J 71:2087–2093

    Article  PubMed  CAS  Google Scholar 

  30. Davidsen J, Rosenkrands I, Christensen D, Vangala A, Kirby D, Perrie Y, Agger E, Andersen P (2005) Characterization of cationic liposomes based on dimethyldioctadecylammonium and synthetic cord factor from M. tuberculosis (trehalose 6,6′-dibehenate)-a novel adjuvant inducing both strong CMI and antibody responses. Biochim Biophys Acta 1718:22–31

    Article  PubMed  CAS  Google Scholar 

  31. de Chasteigner S, Cavé G, Fessi H, Devissaguet J-P, Puisieux F (1998) Freeze-drying of itraconazole-loaded nanosphere suspension: a feasibility study. Drug Dev Res 38:116–124

    Google Scholar 

  32. Demana P, Davies N, Hook S, Rades T (2005) Quil A-lipid powder formulations releasing ISCOMs and related colloidal structures upon hydration. J Control Release 103:45–59

    Article  PubMed  CAS  Google Scholar 

  33. Demento S, Eisenbarth S, Foellmer H, Platt C, Caplan M, Saltzman M, Mellman I, Ledizet M, Fikrig E, Flavell R, Fahmy T (2009) Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy. Vaccine 27:3013–3021

    Article  CAS  Google Scholar 

  34. Denis-Mize K, Dupuis M, Singh M, Woo C, Ugozzoli M, O’Hagan D, Donnelly JI, Ott G, McDonald D (2003) Mechanisms of increased immunogenicity for DNA-based vaccines adsorbed onto cationic microparticles. Cell Immunol 225:12–20

    Article  PubMed  CAS  Google Scholar 

  35. Diwan M, Tafaghodi M, Samuel J (2002) Enhancement of immune responses by co-delivery of a CpG oligodeoxynucleotide and tetanus toxoid in biodegradable nanospheres. J Control Release 85:247–262

    Article  PubMed  CAS  Google Scholar 

  36. Dodane V, Vilivalam V (1998) Pharmaceutical applications of chitosan. Pharm Sci Technol Today 1:246–253

    Article  CAS  Google Scholar 

  37. Domb A, Kumar N, Sheskin T, Bentolila A, Slager J, Teomim D (2002) Biodegradable polymers as drug carrier systems. In: Dumitriu S (ed) Polymeric biomaterials. Marcel Dekker, New York, pp 91–122

    Google Scholar 

  38. Duncan G, Jess T, Mohamed F, Price N, Kelly S, van der Walle C (2005) The influence of protein solubilisation, conformation and size on the burst release from poly(lactide-co-glycolide) microspheres. J Control Release 110:34–48

    Article  PubMed  CAS  Google Scholar 

  39. Eldridge J, Staas J, Meulbroek J, Tice T, Gilley R (1991) Biodegradable and biocompatible poly(DL-lactide-co-glycolide) microspheres as an adjuvant for staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies. Infect Immun 59:2978–2986

    PubMed  CAS  Google Scholar 

  40. Esposito E, Sebben S, Cortesi R, Menegatti E, Nastruzzi C (1999) Preparation and characterization of cationic microspheres for gene delivery. Int J Pharm 189:29–41

    Article  PubMed  CAS  Google Scholar 

  41. Fattal E, Pecquet S, Couvreur P, Andremont A (2002) Biodegradable microparticles for the mucosal delivery of antibacterial and dietary antigens. Int J Pharm 242:15–24

    Article  PubMed  CAS  Google Scholar 

  42. Fearon K, Marshall JD, Abbate C, Subramanian S, Yee P, Gregorio J, Teshima G, Ott G, Tuck S, Van Nest G (2003) A minimal human immunostimulatory CpG motif that potently induces IFN-gamma and IFN-alpha production. Eur J Immunol 33:2114–2159

    Article  PubMed  CAS  Google Scholar 

  43. Feng L, Rong X, Xing Q, Zhou J, Maitani Y, Wang S, Jiang Y, Nagai T (2006) Pharmaceutical and immunological evaluation of a single-dose hepatitis B vaccine using PLGA microspheres. J Control Release 112:35–42

    Article  PubMed  CAS  Google Scholar 

  44. Fessi H, Puisieux F, Devissaguet J, Ammoury N, Benita S (1989) Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 55:1–4

    Article  Google Scholar 

  45. Flynn J, Chan J, Triebold K, Dalton D, Stewart T, Bloom B (1993) An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178:2249–2254

    Article  PubMed  CAS  Google Scholar 

  46. Freytag L, Clements J (2005) Mucosal adjuvants. Vaccine 23:1804–1813

    Article  PubMed  CAS  Google Scholar 

  47. Furr B, Hutchinson F (1985) Biodegradable sustained release formulation of the LH-RH analogue ‘Zoladex’ for the treatment of hormone-responsive tumours. Prog Clin Biol Res 185:143–153

    Google Scholar 

  48. Furukawa T, Matsusue Y, Yasunaga T, Shikinami Y, Okuno M, Nakamura T (2000) Biodegradation behavior of ultra-high-strength hydroxyapatite/poly (-lactide) composite rods for internal fixation of bone fractures. Biomaterials 21:889–898

    Article  PubMed  CAS  Google Scholar 

  49. Gall D (1966) The adjuvant activity of aliphatic nitrogenous bases. Immunology 11:369–386

    PubMed  CAS  Google Scholar 

  50. Gheorghiu M, Lagranderie M, Balazuc A (1996) Stabilisation of BCG vaccines. Dev Biol Stand 87:251–261

    PubMed  CAS  Google Scholar 

  51. Gopferich A (1996) Mechanisms of polymer degradation and erosion. Biomaterials 17:103–114

    Article  PubMed  CAS  Google Scholar 

  52. Hamdy S, Molavi O, Ma Z, Haddadi A, Alshamsan A, Gobti Z, Elhasi S, Samuel J, Lavasanifar A (2008) Co-delivery of cancer-associated antigen and Toll-like receptor 4 ligand in PLGA nanoparticles induces potent CD8+ T cell-mediated anti-tumor immunity. Vaccine 26:5046–5047

    Article  PubMed  CAS  Google Scholar 

  53. Hanafusa S, Matsusue Y, Yasunaga T, Yamamuro T, Oka M, Shikinami Y, Ikada Y (1995) Biodegradable plate fixation of rabbit femoral shaft osteotomies. A comparative study. Clin Orthop Relat Res 315:262–271

    PubMed  Google Scholar 

  54. Harish Prashanth K, Tharanathan R (2007) Chitin/chitosan: modifications and their unlimited application potential an overview. Trends Food Sci Technol 18:117–131

    Article  CAS  Google Scholar 

  55. Heath T, Lopez N, Papahadjopoulos D (1985) The effects of liposome size and surface charge on liposome-mediated delivery of methotrexate-[gamma]-aspartate to cells in vitro. Biochim Biophys Acta 820:74–84

    Article  PubMed  CAS  Google Scholar 

  56. Henriksen-Lacey M, Bramwell V, Christensen D, Agger E, Andersen P, Perrie Y (2010) Liposomes based on dimethyldioctadecylammonium promote a depot effect and enhance immunogenicity of soluble antigen. J Control Release 142:180–186

    Article  PubMed  CAS  Google Scholar 

  57. Hornung V, Bauernfeind F, Halle A, Samstad E, Kono H, Rock K, Fitzgerald K, Latz E (2008) Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 9:847–856

    Article  PubMed  CAS  Google Scholar 

  58. Huang M, Khor E, Lim L (2004) Uptake and cytotoxicity of chitosan molecules and nanoparticles: effects of molecular weight and degree of deacetylation. Pharm Res 21:344–353

    Article  PubMed  CAS  Google Scholar 

  59. Igartua M, Hernandez R, Esquisabel A, Gascon A, Calvo M, Pedraz J (1998) Enhanced immune response after subcutaneous and oral immunization with biodegradable PLGA microspheres. J Control Release 56:63–73

    Article  PubMed  CAS  Google Scholar 

  60. Ishikawa E, Ishikawa T, Morita Y, Toyonaga K, Yamada H, Takeuchi O, Kinoshita T, Akira S, Yoshikai Y, Yamasaki S (2009) Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J Exp Med 206:2879–2888

    Article  PubMed  CAS  Google Scholar 

  61. Jabbal-Gill I, Lin W, Jenkins P, Watts P, Jimenez M, Illum L, Davis S, Wood J, Major D, Minor P (1999) Potential of polymeric lamellar substrate particles (PLSP) as adjuvants for vaccines. Vaccine 18:238–250

    Article  PubMed  CAS  Google Scholar 

  62. Jain R (2000) The manufacturing techniques of various drug loaded biodegradable poly (lactide-co-glycolide) (PLGA) devices. Biomaterials 21:2475–2490

    Article  PubMed  CAS  Google Scholar 

  63. Jalil R, Nixon J (1990) Biodegradable poly (lactic acid) and poly (lactide-coglycolide) microcapsules: problems associated with preparative techniques and release properties. J Microencapsul 7:297–325

    Article  PubMed  CAS  Google Scholar 

  64. Jamshidi K, Hyon S, Ikada Y (1988) Thermal characterization of polylactides. Polymer 29:2229–2234

    Article  CAS  Google Scholar 

  65. Janeway CJ (1989) Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 54:1–13

    Article  PubMed  CAS  Google Scholar 

  66. Jiang W, Gupta R, Deshpande M, Schwendeman S (2005) Biodegradable poly(lactic-co-glycolic acid) microparticles for injectable delivery of vaccine antigens. Adv Drug Deliv Rev 57:391–410

    Article  PubMed  CAS  Google Scholar 

  67. Jilek S, Merkle H, Walter E (2005) DNA-loaded biodegradable microparticles as vaccine delivery systems and their interaction with dendritic cells. Adv Drug Deliv Rev 57:377–390

    Article  PubMed  CAS  Google Scholar 

  68. Johansen P, Moon L, Tamber H, Merkle H, Gander B, Sesardic D (1999) Immunogenicity of single-dose diphtheria vaccines based on PLA/PLGA microspheres in guinea pigs. Vaccine 18:209–215

    Article  PubMed  CAS  Google Scholar 

  69. Jung T, Koneberg R, Hungerer K, Kissel T (2002) Tetanus toxoid microspheres consisting of biodegradable poly(lactide-co-glycolide)- and ABA-triblock-copolymers: immune response in mice. Int J Pharm 234:75–90

    Article  PubMed  CAS  Google Scholar 

  70. Khor E, Lim L (2003) Implantable applications of chitin and chitosan. Biomaterials 24:2339–2349

    Article  PubMed  CAS  Google Scholar 

  71. Kim H, Chung H, Park T (2006) Biodegradable polymeric microspheres with open/closed pores for sustained release of human growth hormone. J Control Release 112:167–174

    Article  PubMed  CAS  Google Scholar 

  72. Kirby C, Gregoriadis G (1984) Preparation of liposomes containing factor VIII for oral treatment of haemophilia. J Microencapsul 1:33–45

    Article  PubMed  CAS  Google Scholar 

  73. Kirby D, Rosenkrands I, Agger E, Andersen P, Coombes A, Perrie Y (2008) PLGA microspheres for the delivery of a novel subunit TB vaccine. J Drug Target 16:282–293

    Article  PubMed  CAS  Google Scholar 

  74. Kirby D, Rosenkrands I, Agger E, Andersen P, Coombes A, Perrie Y (2008) Liposomes act as stronger subunit vaccine adjuvants when compared to microspheres. J Drug Target 16:543–554

    Article  PubMed  CAS  Google Scholar 

  75. Kissel T, Koneberg R (1996) Injectable biodegradable microspheres for vaccine delivery. In: Cohen S, Bernstein H (eds) Microparticulate systems for the delivery of proteins and vaccines. Marcel Dekker, New York, pp 51–88

    Google Scholar 

  76. Konan Y, Gurny R, Allemann E (2002) Preparation and characterization of sterile and freeze-dried sub-200 nm nanoparticles. Int J Pharm 233:239–252

    Article  PubMed  CAS  Google Scholar 

  77. Koster K, Leopold A (1988) Sugars and desiccation tolerance in seeds. Plant Physiol 88:829–832

    Article  PubMed  CAS  Google Scholar 

  78. Langer R, Folkman J (1976) Polymers for the sustained release of proteins and other macromolecules. Nature 263:797–800

    Article  PubMed  CAS  Google Scholar 

  79. Lemoine D, Francois C, Kedzierewicz F, Preat V, Hoffman M, Maincent P (1996) Stability study of nanoparticles of poly(epsilon-caprolactone), poly(D, L-lactide) and poly(D, L-lactide-co-glycolide). Biomaterials 17:2191–2197

    Article  PubMed  CAS  Google Scholar 

  80. Levine H, Slade L (1988) Principles of ‘cryostabilization’ technology from structure/property relationships of carbohydrate/water systems—a review. Cryo-Lett 9:21–63

    CAS  Google Scholar 

  81. Lewis D (1990) Controlled release of bioactive agents from lactide/glycolide polymers. In: Chasin M, Langer R (eds) Biodegradable polymers as drug delivery systems. Marcel Dekker, New York, pp 1–41

    Google Scholar 

  82. Li B, Li S, Tan Y, Stolz D, Watkins S, Block L, Huang L (2000) Lyophilization of cationic lipid-protamine-DNA (LPD) complexes. J Pharm Sci 89:355–364

    Article  PubMed  CAS  Google Scholar 

  83. Linghua Z, Xingshan T, Fengzhen Z (2008) In vivo oral administration effects of various oligodeoxynucleotides containing synthetic immunostimulatory motifs in the immune response to pseudorabies attenuated virus vaccine in newborn piglets. Vaccine 26:224–233

    Article  PubMed  CAS  Google Scholar 

  84. Lloyd J (2000) Technologies for vaccine delivery in the 21st century. Department of Vaccines and Biologicals, World Health Organisation, Geneva, Switzerland

    Google Scholar 

  85. Luzardo-Alvarez A, Blarer N, Peter K, Romero J, Reymond C, Corradin G, Gander B (2005) Biodegradable microspheres alone do not stimulate murine macrophages in vitro, but prolong antigen presentation by macrophages in vitro and stimulate a solid immune response in mice. J Control Release 109:62–76

    Article  PubMed  CAS  Google Scholar 

  86. Mandal B, Kempf M, Merkle H, Walter E (2004) Immobilisation of GM-CSF onto particulate vaccine carrier systems. Int J Pharm 269:259–265

    Article  PubMed  CAS  Google Scholar 

  87. Manning M, Patel K, Borchardt R (1989) Stability of protein pharmaceuticals. Pharm Res 6:903–918

    Article  PubMed  CAS  Google Scholar 

  88. McCluskie M, Weeratna R, Krieg A, Davis H (2000) CpG DNA is an effective oral adjuvant to protein antigens in mice. Vaccine 19:950–957

    Article  PubMed  CAS  Google Scholar 

  89. Miyajima K, Tomita K, Nakagaki M (1986) Effect of saccharides on the freezing and thawing of liposome dispersion. Chem Pharm Bull 34:2689–2697

    Article  PubMed  CAS  Google Scholar 

  90. Mohammed A, Bramwell V, Coombes A, Perrie Y (2006) Lyophilisation and sterilisation of liposomal vaccines to produce stable and sterile products. Methods 40:30–38

    Article  PubMed  CAS  Google Scholar 

  91. Mohammed A, Coombes A, Perrie Y (2007) Amino acids as cryoprotectants for liposomal delivery systems. Eur J Pharm Sci 30:406–413

    Article  PubMed  CAS  Google Scholar 

  92. Mollenkopf H, Dietrich G, Fensterle J, Grode L, Diehl K, Knapp B, Singh M, O’Hagan D, Ulmer J, Kaufmann S (2004) Enhanced protective efficacy of a tuberculosis DNA vaccine by adsorption onto cationic PLG microparticles. Vaccine 22:2690–2695

    Article  PubMed  CAS  Google Scholar 

  93. Mori T, Okumura M, Matsuura M, Ueno K, Tokura S, Okamoto Y, Minami S, Fujinaga T (1997) Effects of chitin and its derivatives on the proliferation and cytokine production of fibroblasts in vitro. Biomaterials 18:947–951

    Article  PubMed  CAS  Google Scholar 

  94. Morokata T, Ishikawaa J, Yamada T (2000) Antigen dose defines T helper 1 and T helper 2 responses in the lungs of C57BL/6 and BALB/c mice independently of splenic responses. Immunol Lett 72:119–126

    Article  PubMed  CAS  Google Scholar 

  95. Moschos S, Bramwell V, Somavarapu S, Alpar H (2004) Adjuvant synergy: the effects of nasal coadministration of adjuvants. Immunol Cell Biol 82:628–637

    Article  PubMed  CAS  Google Scholar 

  96. Mosmann T, Sad S (1996) The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 17:138–146

    Article  PubMed  CAS  Google Scholar 

  97. Myschik J, Lendemans D, McBurney W, Demana P, Hook S, Rades T (2006) On the preparation, microscopic investigation and application of ISCOMs. Micron 37:724–734

    Article  PubMed  CAS  Google Scholar 

  98. Nishimura K, Nishimura S, Seo H, Nishi N, Tokura S, Azuma I (1987) Effect of multiporous microspheres derived from chitin and partially deacetylated chitin on the activation of mouse peritoneal macrophages. Vaccine 5:136–140

    Article  PubMed  CAS  Google Scholar 

  99. Nykamp G, Carstensen U, Muller B (2002) Jet milling a new technique for microparticle preparation. Int J Pharm 242:79–86

    Article  PubMed  CAS  Google Scholar 

  100. Ogawa Y, Yamamoto M, Okada H, Yashiki T, Shimamoto T (1988) A new technique to efficiently entrap leuprolide acetate into microcapsules of polylactic acid or copoly(lactic/glycolic) acid. Chem Pharm Bull 36:1095–1103

    Article  PubMed  CAS  Google Scholar 

  101. O’Hagan D, MacKichan M, Singh M (2001) Recent developments in adjuvants for vaccines against infectious diseases. Biomol Eng 18:69–85

    Article  PubMed  Google Scholar 

  102. O’Hagan D, Rahman D, McGee J, Jeffery H, Davies M, Williams P, Davis S, Challacombe S (1991) Biodegradable microparticles as controlled release antigen delivery systems. Immunology 73:239–242

    PubMed  Google Scholar 

  103. O’Hagan D, Singh M, Dong C, Ugozzoli M, Berger K, Glazer E, Selby M, Wininger M, Ng P, Crawford K, Paliard X, Coates S, Houghton M (2004) Cationic microparticles are a potent delivery system for a HCV DNA vaccine. Vaccine 23:672–680

    Article  PubMed  CAS  Google Scholar 

  104. Olds G, Chedid L, Lederer E, Mahmoud A (1980) Induction of resistance to Schistosoma-mansoni by natural cord factor and synthetic lower homologs. J Infect Dis 141:473–478

    Article  PubMed  CAS  Google Scholar 

  105. Ozaki K, Hayashi M (1998) Effect of cycloinulohexaose with additives on the freeze-drying of liposome. Int J Pharm 160:219–227

    Article  CAS  Google Scholar 

  106. Patel V, Patel M, Patel R (2005) Chitosan: a unique pharmaceutical excipient. Drug Deliv Technol 5:30–40

    CAS  Google Scholar 

  107. Peluso G, Petillo O, Ranieri M, Santin M, Ambrosic L, Calabro D, Avallone B, Balsamo G (1994) Chitosan-mediated stimulation of macrophage function. Biomaterials 15:1215–1220

    Article  PubMed  CAS  Google Scholar 

  108. Perrie Y, Kirby D, Bramwell V, Mohammed A (2007) Recent developments in particulate-based vaccines. Recent Pat Drug Deliv Formul 1:117–130

    Article  PubMed  CAS  Google Scholar 

  109. Perrin D, English J (1997) Polyglycolide and polylactide. In: Domb A, Kost J, Wiseman D (eds) Handbook of biodegradable polymers. Harwood Academic Publishers, Amsterdam, pp 3–28

    Google Scholar 

  110. Petaja T, Keranen H, Karppa T, Kawa A, Lantela S, Siitari-Mattila M, Levanen H, Tocklin T, Godeaux O, Lehtinen M, Dubin G (2009) Immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in healthy boys aged 10-18 years. J Adolesc Health 44:33–40

    Article  PubMed  Google Scholar 

  111. Peyre M, Fleck R, Hockley D, Gander B, Sesardic D (2004) In vivo uptake of an experimental microencapsulated diphtheria vaccine following sub-cutaneous immunisation. Vaccine 22:2430–2437

    Article  PubMed  CAS  Google Scholar 

  112. Pimm M, Baldwin R, Polonsky J, Lederer E (1979) Immunotherapy of an ascitic rat hepatoma with cord factor (trehalose-6, 6′-dimycolate) and synthetic analogs. Int J Cancer 24:780–785

    Article  PubMed  CAS  Google Scholar 

  113. Playfair J, Bancroft G (2004) Infection and immunity, 2nd edn. Oxford University Press, Oxford

    Google Scholar 

  114. Preis I, Langer R (1979) A single-step immunization by sustained antigen release. J Immunol Methods 28:193–197

    Article  PubMed  CAS  Google Scholar 

  115. Quaglia F, De R, Granata E, Ungaro F, Fattal E, Immacolata La Rotonda M (2003) Feeding liquid, non-ionic surfactant and cyclodextrin affect the properties of insulin-loaded poly(lactide-co-glycolide) microspheres prepared by spray-drying. J Control Release 86:267–278

    Article  PubMed  CAS  Google Scholar 

  116. Rafati H, Coombes A, Adler J, Holland J, Davis S (1997) Protein-loaded poly(-lactide-co-glycolide) microparticles for oral administration: formulation, structural and release characteristics. J Control Release 43:89–102

    Article  CAS  Google Scholar 

  117. Ravi Kumar M, Bakowsky U, Lehr C (2004) Preparation and characterization of cationic PLGA nanospheres as DNA carriers. Biomaterials 25:1771–1777

    Article  PubMed  CAS  Google Scholar 

  118. Ren J, Hong H, Song J, Ren T (2005) Particle size and distribution of biodegradable poly-D, L-lactide-co-poly(ethylene glycol) block polymer nanoparticles prepared by nanoprecipitation. J Appl Poly Sci 98:1884–1890

    Article  CAS  Google Scholar 

  119. Roman B, Irache J, Gomez S, Tsapis N, Gamazo C, Espuelas M (2008) Co-encapsulation of an antigen and CpG oligonucleotides into PLGA microparticles by TROMS technology. Eur J Pharm Biopharm 70:98–108

    Article  CAS  Google Scholar 

  120. Rosas J, Pedraz J, Hernandez R, Gascon A, Igartua M, Guzman F, Rodriguez R, Cortes J, Patarroyo M (2002) Remarkably high antibody levels and protection against P. falciparum malaria in Aotus monkeys after a single immunisation of SPf66 encapsulated in PLGA microspheres. Vaccine 20:1707–1710

    Article  PubMed  CAS  Google Scholar 

  121. Rosenkrands I, Agger E, Olsen A, Korsholm K, Andersen C, Jensen K, Andersen P (2005) Cationic liposomes containing mycobacterial lipids—a new powerful Th1 adjuvant system. Infect Immun 73:5817–5826

    Article  PubMed  CAS  Google Scholar 

  122. Roy D, Guillon X, Lescure F, Couvreur P, Bru N, Breton P (1997) On shelf stability of freeze-dried poly(methylidene malonate 2.1.2) nanoparticles. Int J Pharm 148:165–175

    Article  CAS  Google Scholar 

  123. Saez A, Guzman M, Molpeceres J, Aberturas M (2000) Freeze-drying of polycaprolactone and poly(D, L-lactic-glycolic) nanoparticles induce minor particle size changes affecting the oral pharmacokinetics of loaded drugs. Eur J Pharm Biopharm 50:379–387

    Article  PubMed  CAS  Google Scholar 

  124. Sarti F, Perera G, Hintzen F, Kotti K, Karageorgiou V, Kammona O, Kiparissides C, Bernkop-Schnurch A (2011) In vivo evidence of oral vaccination with PLGA nanoparticles containing the immunostimulant monophosphoryl. Biomaterials 32:4052–4057

    Article  PubMed  CAS  Google Scholar 

  125. Sartia F, Pereraa G, Hintzena F, Kottib K, Karageorgioub V, Kammonab O, Kiparissidesb C, Bernkop-Schnurcha A (2011) In vivo evidence of oral vaccination with PLGA nanoparticles containing the immunostimulant monophosphoryl lipid A. Biomaterials 32:4052–4057

    Article  CAS  Google Scholar 

  126. Schoenen H, Bodendorfer B, Hitchens K, Manzanero S, Werninghaus K, Nimmerjahn F, Agger E, Stenger S, Andersen P, Ruland J, Brown G, Wells C, Lang R (2010) Cutting edge: mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. J Immunol 184:2756–2760

    Article  PubMed  CAS  Google Scholar 

  127. Schondorf I, Banzhoff A, Nicolay U, Diaz-Mitoma F (2007) Overcoming the need for a cold chain with conjugated meningococcal Group C vaccine: a controlled, randomized, double-blind study in toddlers on the safety and immunogenicity of Menjugate, stored at room temperature for 6 months. Vaccine 25:1175–1182

    Article  PubMed  CAS  Google Scholar 

  128. Seville P, Kellaway I, Birchall J (2002) Preparation of dry powder dispersions for non-viral gene delivery by freeze-drying and spray-drying. J Gene Med 4:428–437

    Article  PubMed  CAS  Google Scholar 

  129. Singh A, Kasinath B, Lewis E (1992) Interaction of polycations with cell-surface negative charges of epithelial cells. Biochim Biophys Acta 1120:337–342

    Article  PubMed  CAS  Google Scholar 

  130. Sinha V, Trehan A (2003) Biodegradable microspheres for protein delivery. J Control Release 90:261–280

    Article  PubMed  CAS  Google Scholar 

  131. Smith Korsholm K, Agger E, Foged C, Christensen D, Dietrich J, Andersen C, Geisler C, Andersen P (2007) The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes. Immunology 121:216–226

    Article  CAS  Google Scholar 

  132. Storni T, Kundig T, Senti G, Johansen P (2005) Immunity in response to particulate antigen-delivery systems. Adv Drug Deliv Rev 57:333–355

    Article  PubMed  CAS  Google Scholar 

  133. Strong P, Clark H, Reid K (2002) Intranasal application of chitin microparticles down-regulates symptoms of allergic hypersensitivity to Dermatophagoides pteronyssinus and Aspergillus fumigatus in murine models of allergy. Clin Exp Allergy 32:1794–1800

    Article  PubMed  CAS  Google Scholar 

  134. Sun W, Leopold A, Crowe L, Crowe J (1996) Stability of dry liposomes in sugar glasses. Biophys J 70:1769–1776

    Article  PubMed  CAS  Google Scholar 

  135. Tabata Y, Ikada Y (1988) Effect of the size and surface charge of polymer microspheres on their phagocytosis by macrophage. Biomaterials 9:356–362

    Article  PubMed  CAS  Google Scholar 

  136. Tabata Y, Ikada Y (1988) Macrophage phagocytosis of biodegradable microspheres composed of L-lactic acid/glycolic acid homo- and copolymers. J Biomed Mater Res 22:837–858

    Article  PubMed  CAS  Google Scholar 

  137. Tamber H, Johansen P, Merkle H, Gander B (2005) Formulation aspects of biodegradable polymeric microspheres for antigen delivery. Adv Drug Deliv Rev 57:357–376

    Article  PubMed  CAS  Google Scholar 

  138. Tice T, Cowsar DB (1984) Biodegradable controlled-release parenteral systems. J Pharm Technol 8:26–31

    CAS  Google Scholar 

  139. Vangala A, Bramwell V, McNeil S, Christensen D, Agger E, Perrie Y (2007) Comparison of vesicle based antigen delivery systems for delivery of hepatitis B surface antigen. J Control Release 119:102–110

    Article  PubMed  CAS  Google Scholar 

  140. Vila A, Sanchez A, Tobio M, Calvo P, Alonso M (2002) Design of biodegradable particles for protein delivery. J Control Release 78:15–24

    Article  PubMed  CAS  Google Scholar 

  141. Vrancken M, Claeys D (1970) Method for encapsulating water and compounds in aqueous phase by extraction. US Patent 3523907

    Google Scholar 

  142. Werninghaus K, Babiak A, Groß O, Holscher C, Dietrich H, Agger E, Mages J, Mocsai A, Schoenen H, Finger K, Nimmerjahn F, Brown G, Kirschning C, Heit A, Andersen P, Wagner H, Ruland J, Lang R (2009) Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRγ-Syk-Card9-dependent innate immune activation. J Exp Med 206:89–97

    Article  PubMed  CAS  Google Scholar 

  143. Wischke C, Borchert H, Zimmermann J, Siebenbrodt I, Lorenzen D (2006) Stable cationic microparticles for enhanced model antigen delivery to dendritic cells. J Control Release 114:359–368

    Article  PubMed  CAS  Google Scholar 

  144. Ahsan, F., Rivas, I.P., Khan, M.A., Torres Suarez, A.I. (2002) Targeting to macrophages: role of physicochemical properties of particulate carriers–liposomes and microspheres–on the phagocytosis by macrophages. J. Control Release, 79, 29–40

    Article  PubMed  CAS  Google Scholar 

  145. Alpar, H.O., Somavarapu, S., Atuah, K.N., Bramwell, V.W. (2005) Biodegradable mucoadhesive particulates for nasal and pulmonary antigen and DNA delivery. Advanced Drug Delivery Reviews, 57, 411–430

    Article  PubMed  CAS  Google Scholar 

  146. Brunner, R., Jensen-Jarolim, E., Pali-Schöll, I. (2010) The ABC of clinical and experimental adjuvants—A brief overview. Immunology Letters, 128(1), 29–35

    Article  PubMed  CAS  Google Scholar 

  147. Brandt, L., Elhay, M., Rosenkrands, I., Lindblad, E.B., Andersen, P. (2000) ESAT-6 subunit vaccination against Mycobacterium tuberculosis. Infect. Immun., 68, 791–795

    Article  PubMed  CAS  Google Scholar 

  148. Crowe, J.H., Leslie, S.B., Crowe, L.M. (1994a) Is vitrification sufficient to preserve liposomes during freeze-drying? Cryobiology, 31, 355–366

    Article  PubMed  CAS  Google Scholar 

  149. Davis, H.L., Weeratna, R., Waldschmidt, T.J., Tygrett, L., Schorr, J., Krieg, A.M. (1998) CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen. J. Immunol., 160, 870–876

    PubMed  CAS  Google Scholar 

  150. Hamdy, S., Haddadi, A., Somayaji, V., Ruan, D., Samuel, J. (2007) Pharmaceutical analysis of synthetic lipid A-based vaccine adjuvants in poly (d,l-lactic-co-glycolic acid) nanoparticle formulations. Journal of Pharmaceutical and Biomedical Analysis, 44(4), 914–92

    Article  PubMed  CAS  Google Scholar 

  151. Holten-Andersen, L., Doherty, T.M., Korsholm, K.S., Andersen, P. (2004) Combination of the cationic surfactant dimethyl dioctadecyl ammonium bromide and synthetic mycobacterial cord factor as an efficient adjuvant for tuberculosis subunit vaccines. Infect. Immun., 72, 1608–1617

    Article  PubMed  CAS  Google Scholar 

  152. Illum, L., Farraj, N.F., Davis, S.S. (1994) Chitosan as a Novel Nasal Delivery System for Peptide Drugs. Pharmaceutical Research, 11, 1186–1189

    Article  PubMed  CAS  Google Scholar 

  153. Klinguer, C., Beck, A., De-Lys, P., Bussat, M.C., Blaecke, A., Derouet, F., Bonnefoy, J.Y., Nguyen, T.N., Corvaia, N., Velin, D. (2001) Lipophilic quaternary ammonium salt acts as a mucosal adjuvant when co-administered by the nasal route with vaccine antigens. Vaccine, 19, 4236–4244

    Article  PubMed  CAS  Google Scholar 

  154. Lindblad, E.B., Elhay, M.J., Silva, R., Appelberg, R., Andersen, P. (1997) Adjuvant modulation of immune responses to tuberculosis subunit vaccines. Infect. Immun., 65, 623–629

    PubMed  CAS  Google Scholar 

  155. McCluskie, M.J., Davis, H.L. (1998) CpG DNA is a potent enhancer of systemic and mucosal immune responses against hepatitis B surface antigen with intranasal administration to mice. J. Immunol., 161, 4463–4466

    PubMed  CAS  Google Scholar 

  156. Singh, M., Ugozzoli, M., Briones, M., Kazzaz, J., Soenawan, E., O'Hagan, D.T. (2003) The effect of CTAB concentration in cationic PLG microparticles on DNA adsorption and in vivo performance. Pharm. Res., 20, 247–251

    Article  PubMed  CAS  Google Scholar 

  157. Snippe, H., de Reuver, M.J., Beunder, J.W., van der Meer, J.B., van Wichen, D.F., Willers, J.M. (1982) Delayed-type hypersensitivity in rabbits. Comparison of the adjuvants dimethyl dioctadecyl ammonium bromide and Freund's complete adjuvant. Int. Arch. Allergy Appl. Immunol., 67, 139–144

    CAS  Google Scholar 

  158. Ulrich, J.T., Myers, K.R. (1995) Monophosphoryl lipid A as an adjuvant. Past experiences and new directions. Pharm. Biotechnol., 6, 495–524

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Life and Health Sciences, Aston University, Birmingham, UK

    Daniel J. Kirby & Randip Kaur

  2. School of Life and Health Sciences, University of Aston, Birmingham, UK

    Yvonne Perrie

Authors
  1. Daniel J. Kirby
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Randip Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yvonne Perrie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel J. Kirby .

Editor information

Editors and Affiliations

  1. Aston Pharmacy School, School of Life and Health Sciences, University of Aston, Aston Triangle, Birmingham, B4 7ET, United Kingdom

    Darren R. Flower

  2. Aston Pharmacy School, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, United Kingdom

    Yvonne Perrie

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kirby, D.J., Kaur, R., Perrie, Y. (2013). Formulation and Characterisation of PLGA Microspheres as Vaccine Adjuvants. In: Flower, D., Perrie, Y. (eds) Immunomic Discovery of Adjuvants and Candidate Subunit Vaccines. Immunomics Reviews:, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5070-2_13

Download citation

Publish with us

Policies and ethics

Search

Navigation