Skip to main content

Biodegradable Nanoparticles as Vaccine Adjuvants and Delivery Systems: Regulation of Immune Responses by Nanoparticle-Based Vaccine

  • Chapter
  • First Online:
Polymers in Nanomedicine

Part of the book series: Advances in Polymer Science ((POLYMER,volume 247))

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

Abbreviations

APCs:

Antigen-presenting cells

BSA:

Bovine serum albumin

CFA:

Complete Freund’s adjuvant

CLSM:

Confocal laser scanning microscopy

CT:

Chitosan

CTL:

Cytotoxic T lymphocyte

DCC:

N,N-Dicyclohexyl carbodiimide

DCs:

Dendritic cells

DDS:

Drug delivery system

DLS:

Dynamic light scattering

FCM:

Flow cytometry

HBcAg:

Hepatitis B core antigen

HIV:

Human immunodeficiency virus

HOBt:

1-Hydroxybenzotriazole

HTLV-I:

Human T-cell leukemia virus type-I

LPS:

Lipopolysaccharide

MHC:

Major histocompatibility complex

MPLA:

Monophospholipid A

o/w:

Oil-in-water

OVA:

Ovalbumin

OVA-NPs:

OVA encapsulating within γ-PGA-Phe nanoparticles

PCL:

Poly(ε-caprolactone)

pDNA:

Plasmid DNA

PEI:

Polyethylenimine

PGA:

Poly(glycolic acid)

PHB:

Poly(hydroxybutyrate)

Phe:

l-Phenylalanine

PIC:

Polyion complex

PLA:

Poly(lactic acid)

PLGA:

Poly(lactide-co-glycolide)

SAXS:

Small angle X-ray scattering

SEM:

Scanning electron microscopy

TEM:

Transmission electron microscopy

Th:

T helper

TLR:

Toll-like receptor

Trp:

l-Tryptophan

w/o/w:

Water-in-oil-in-water

γ-PGA:

Poly(γ-glutamic acid)

γ-PGA-Phe:

γ-PGA-graft-Phe copolymer

ε-PL:

Poly(ε-lysine)

ε-PL-CHS:

ε-PL-graft-cholesterol hydrogen succinate

References

  1. Zhao Z, Leong KW (1996) Controlled delivery of antigens and adjuvants in vaccine development. J Pharm Sci 85:1261–1270

    CAS  Google Scholar 

  2. Singh M, O’Hagan DT (2002) Recent advances in vaccine adjuvants. Pharm Res 19:715–728

    CAS  Google Scholar 

  3. Singh M, O'Hagan DT (1999) Advances in vaccine adjuvants. Nat Biotechnol 17:1075–1081

    CAS  Google Scholar 

  4. O'Hagan DT, Rappuoli R (2004) Novel approaches to vaccine delivery. Pharm Res 21:1519–1530

    Google Scholar 

  5. Peek LJ, Middaugh CR, Berkland C (2008) Nanotechnology in vaccine delivery. Adv Drug Deliv Rev 60:915–928

    CAS  Google Scholar 

  6. Ramon G (1924) Sur la toxine et surranatoxine diphtheriques. Ann Inst Pasteur 38:1–10

    CAS  Google Scholar 

  7. Gupta RK (1998) Aluminum compounds as vaccine adjuvants. Adv Drug Deliv Rev 32:155–172

    CAS  Google Scholar 

  8. Brewer JM (2006) (How) do aluminium adjuvants work? Immunol Lett 102:10–15

    CAS  Google Scholar 

  9. Soppimath KS, Aminabhavi TM, Kulkarni AR et al (2001) Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70:1–20

    CAS  Google Scholar 

  10. Hans ML, Lowman AM (2002) Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 6:319–327

    CAS  Google Scholar 

  11. Greenland JR, Letvin NL (2007) Chemical adjuvants for plasmid DNA vaccines. Vaccine 25:3731–3741

    CAS  Google Scholar 

  12. Kakizawa Y, Kataoka K (2002) Block copolymer micelles for delivery of gene and related compounds. Adv Drug Deliv Rev 54:203–222

    CAS  Google Scholar 

  13. Zhang L, Eisenberg A (1995) Multiple morphologies of crew-cut aggregates of polystyrene-b-poly(acrylic acid) block copolymers. Science 1268:1728–1731

    Google Scholar 

  14. Dou H, Jiang M, Peng H et al (2003) pH-dependent self-assembly: micellization and micelle-hollow-sphere transition of cellulose-based copolymers. Angew Chem Int Ed 42:1516–1519

    CAS  Google Scholar 

  15. Reihs T, Muller M, Lunkwitz K (2004) Preparation and adsorption of refined polyelectrolyte complex nanoparticles. J Colloid Interface Sci 271:69–79

    CAS  Google Scholar 

  16. Kang N, Perron ME, Prudhomme RE et al (2005) Stereocomplex block copolymer micelles: core-shell nanostructures with enhanced stability. Nano Lett 5:315–319

    CAS  Google Scholar 

  17. Panyam J, Labhasetwar V (2003) Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 55:329–347

    CAS  Google Scholar 

  18. Torchilin VP (2006) Multifunctional nanocarriers. Adv Drug Deliv Rev 58:1532–1555

    CAS  Google Scholar 

  19. Vasir JK, Labhasetwar V (2007) Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv Drug Deliv Rev 59:718–728

    CAS  Google Scholar 

  20. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252

    CAS  Google Scholar 

  21. Gamvrellis A, Leong D, Hanley JC et al (2004) Vaccines that facilitate antigen entry into dendritic cells. Immunol Cell Biol 82:506–516

    CAS  Google Scholar 

  22. Harding CV, Song R (1994) Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules. J Immunol 153:4925–4933

    CAS  Google Scholar 

  23. Wang X, Akagi T, Akashi M et al (2007) Development of core-corona type polymeric nanoparticles as an anti-HIV-1 vaccine. Mini-Rev Org Chem 4:281–290

    Google Scholar 

  24. Foged C, Brodin B, Frokjaer S et al (2005) Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model. Int J Pharm 298:315–322

    CAS  Google Scholar 

  25. Kanchan V, Panda AK (2007) Interactions of antigen-loaded polylactide particles with macrophages and their correlation with the immune response. Biomaterials 28:5344–5357

    CAS  Google Scholar 

  26. O'Hagan DT, Jeffery H, Davis SS (1994) The preparation and characterization ofpoly(lactide-co-glycolide) microparticles: III. Microparticle/polymer degradation rates and the in vitro release of a model protein. Int J Pharm 103:37–45

    Google Scholar 

  27. Li X, Deng X, Yuan M et al (2000) In vitro degradation and release profiles of poly-DL-lactide-poly(ethylene glycol) microspheres with entrapped proteins. J Appl Polym Sci 78:140–148

    CAS  Google Scholar 

  28. Liggins RT, Burt HM (2001) Paclitaxel loaded poly(L-lactic acid) microspheres: properties of microspheres made with low molecular weight polymers. Int J Pharm 222:19–33

    CAS  Google Scholar 

  29. Lemoine D, Francois C, Kedzierewicz F et al (1996) Stability study of nanoparticles of poly(ε-caprolactone), poly(D, L-lactide) and poly(D, L-lactide-co-glycolide). Biomaterials 17:2191–2197

    CAS  Google Scholar 

  30. Jiang W, Gupta RK, Deshpande MC et al (2005) Biodegradable poly(lactic-co-glycolic acid) microparticles for injectable delivery of vaccine antigens. Adv Drug Deliv Rev 57:391–410

    CAS  Google Scholar 

  31. Mohamed F, van der Walle CF (2008) Engineering biodegradable polyester particles with specific drug targeting and drug release properties. J Pharm Sci 97:71–87

    CAS  Google Scholar 

  32. Kumari A, Yadav SK, Yadav SC (2009) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B 75:1–18

    Google Scholar 

  33. O'Donnell PB, McGinity JW (1997) Preparation of microspheres by the solvent evaporation technique. Adv Drug Deliv Rev 28:25–42

    Google Scholar 

  34. Lü JM, Wang X, Marin-Muller C et al (2009) Current advances in research and clinical applications of PLGA-based nanotechnology. Expert Rev Mol Diagn 9:325–341

    Google Scholar 

  35. Gaucher G, Dufresne MH, Sant VP et al (2005) Block copolymer micelles: preparation, characterization and application in drug delivery. J Control Release 109:169–188

    CAS  Google Scholar 

  36. Letchford K, Burt H (2007) A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes. Eur J Pharm Biopharm 65:259–269

    CAS  Google Scholar 

  37. Holowka EP, Pochan DJ, Deming TJ (2005) Charged polypeptide vesicles with controllable diameter. J Am Chem Soc 127:12423–12428

    CAS  Google Scholar 

  38. Matsusaki M, Hiwatari K, Higashi M et al (2004) Stably-dispersed and surface-functional bionanoparticles prepared by self-assembling amphipathic polymers of hydrophilic poly(γ-glutamic acid) bearing hydrophobic amino acids. Chem Lett 33:398–399

    CAS  Google Scholar 

  39. Matsusaki M, Fuchida T, Kaneko T et al (2005) Self-assembling bionanoparticles of poly(ε-lysine) bearing cholesterol as a biomesogen. Biomacromolecules 6:2374–2379

    CAS  Google Scholar 

  40. Arimura H, Ohya Y, Ouchi T (2005) Formation of core-shell type biodegradable polymeric micelles from amphiphilic poly(aspartic acid)-block-polylactide diblock copolymer. Biomacromolecules 6:720–725

    CAS  Google Scholar 

  41. Akiyoshi K, Ueminami A, Kurumada S et al (2000) Self-association of cholesteryl-bearing poly(L-lysine) in water and control of its secondary structure by host − guest interaction with cyclodextrin. Macromolecules 33:6752–6756

    CAS  Google Scholar 

  42. Holowka EP, Sun VZ, Kamei DT et al (2007) Polyarginine segments in block copolypeptides drive both vesicular assembly and intracellular delivery. Nat Mater 6:52–57

    CAS  Google Scholar 

  43. Jeong JH, Kang HS, Yang SR et al (2003) Polymer micelle-like aggregates of novel amphiphilic biodegradable poly(asparagine) grafted with poly(caprolactone). Polymer 44:583–591

    CAS  Google Scholar 

  44. Kataoka K, Matsumoto T, Yokoyama M et al (2000) Doxorubicin-loaded poly(ethylene glycol)-poly(β-benzyl-L-aspartate) copolymer micelles: their pharmaceutical characteristics and biological significance. J Control Release 64:143–153

    CAS  Google Scholar 

  45. Lin J, Zhang S, Chen T et al (2007) Micelle formation and drug release behavior of polypeptide graft copolymer and its mixture with polypeptide block copolymer. Int J Pharm 336:49–57

    CAS  Google Scholar 

  46. Lee ES, Shin HJ, Na K et al (2003) Poly(L-histidine)-PEG block copolymer micelles and pH-induced destabilization. J Control Release 90:363–374

    CAS  Google Scholar 

  47. Kubota H, Matsunobu T, Uotani K et al (1993) Production of poly(γ-glutamic acid) by Bacillus subtilis F-2-01. Biosci Biotechnol Biochem 57:1212–1213

    CAS  Google Scholar 

  48. King EC, Watkins WJ, Blacker AJ et al (1998) Covalent modification in aqueous solution of poly-γ-D-glutamic acid from Bacillus licheniformis. J Polym Sci A: Polym Chem 36:1995–1999

    CAS  Google Scholar 

  49. Morillo M, Martinez de Ilarduya A, Munoz-Guerra S (2001) Comblike alkyl esters of biosynthetic poly(γ-glutamic acid). 1. Synthesis and characterization. Macromolecules 34:7868–7875

    CAS  Google Scholar 

  50. Prodhomme EJF, Tutt AL, Glennie MJ et al (2003) Multivalent conjugates of poly-γ-D-glutamic acid from Bacillus licheniformis with antibody F(ab') and glycopeptide ligands. Bioconjug Chem 14:1148–1155

    CAS  Google Scholar 

  51. Tachibana Y, Kurisawa M, Uyama H et al (2003) Thermo- and pH-responsive biodegradable poly(α-N-substituted γ-glutamine)s. Biomacromolecules 4:1132–1134

    CAS  Google Scholar 

  52. Shimokuri T, Kaneko T, Serizawa T et al (2004) Preparation and thermosensitivity of naturally occurring polypeptide poly(γ-glutamic acid) derivatives modified by alkyl groups. Macromol Biosci 4:407–411

    CAS  Google Scholar 

  53. Oppermann FB, Fickaitz S, Steinbiichel A (1998) Biodegradation of polyamides. Polym Degrad Stab 59:337–344

    CAS  Google Scholar 

  54. Obst M, Steinbuchel A (2004) Microbial degradation of poly(amino acid)s. Biomacromolecules 5:1166–1176

    CAS  Google Scholar 

  55. Schneerson R, Kubler-Kielb J, Liu TY et al (2003) Poly(γ-D-glutamic acid) protein conjugates induce IgG antibodies in mice to the capsule of Bacillus anthracis: a potential addition to the anthrax vaccine. Proc Natl Acad Sci USA 100:8945–8950

    CAS  Google Scholar 

  56. Rhie GE, Roehrl MH, Mourez M et al (2003) A dually active anthrax vaccine that confers protection against both bacilli and toxins. Proc Natl Acad Sci USA 100:10925–10930

    CAS  Google Scholar 

  57. Wang TT, Fellows PF, Leighton TJ et al (2004) Induction of opsonic antibodies to the gamma-D-glutamic acid capsule of Bacillus anthracis by immunization with a synthetic peptide-carrier protein conjugate. FEMS Immunol Med Microbiol 40:231–237

    Google Scholar 

  58. Joyce J, Cook J, Chabot D et al (2006) Immunogenicity and protective efficacy of Bacillus anthracis poly-γ-D-glutamic acid capsule covalently coupled to a protein carrier using a novel triazine-based conjugation strategy. J Biol Chem 281:4831–4843

    CAS  Google Scholar 

  59. Kubler-Kielb J, Liu TY, Mocca C et al (2006) Additional conjugation methods and immunogenicity of Bacillus anthracis poly-γ-D-glutamic acid-protein conjugates. Infect Immun 74:4744–4749

    CAS  Google Scholar 

  60. Shih IL, Van YT (2001) The production of poly(γ-glutamic acid) from microorganisms and its various application. Bioresource Technol 79:207–225

    CAS  Google Scholar 

  61. Kaneko T, Higashi M, Matsusaki M et al (2005) Self-assembled soft nanofibrils of amphipathic polypeptides and their morphological transformation. Chem Mater 17:2484–2486

    CAS  Google Scholar 

  62. Akagi T, Wang X, Uto T et al (2007) Protein direct delivery to dendritic cells using nanoparticles based on amphiphilic poly(amino acid) derivatives. Biomaterials 28:3427–3436

    CAS  Google Scholar 

  63. Kim H, Akagi T, Akashi M (2009) Preparation of size tunable amphiphilic poly(amino acid) nanoparticles. Macromol Biosci 9:842–848

    CAS  Google Scholar 

  64. Bodnar M, Kjoniksen AL, Molnar RM et al (2008) Nanoparticles formed by complexation of poly-γ-glutamic acid with lead ions. J Hazard Mater 153:1185–1192

    CAS  Google Scholar 

  65. Radu JEF, Novak L, Hartmann JF et al (2008) Structural and dynamical characterization of poly-γ-glutamic acid-based cross-linked nanoparticles. Colloid Polym Sci 286:365–376

    CAS  Google Scholar 

  66. Shih IL, Shen MH, Van YT (2006) Microbial synthesis of poly(ε-lysine) and its various applications. Bioresour Technol 97:1148–1159

    CAS  Google Scholar 

  67. Saimura M, Takehara M, Mizukami S et al (2008) Biosynthesis of nearly monodispersed poly(ε-L-lysine) in Streptomyces species. Biotechnol Lett 30:377–385

    CAS  Google Scholar 

  68. Harada A, Kawamura M, Matsuo T et al (2006) Synthesis and characterization of head-tail type polycation block copolymer as non-viral gene vector. Bioconjug Chem 17:3–5

    CAS  Google Scholar 

  69. Wagner E, Kloeckner J (2006) Gene delivery using polymer therapeutics. Adv Polym Sci 192:135–173

    CAS  Google Scholar 

  70. Nguyen DN, Green JJ, Chan JM et al (2009) Polymeric materials for gene delivery and DNA vaccination. Adv Mater 21:847–867

    CAS  Google Scholar 

  71. Tousignan JD, Gates AL, Ingram LA et al (2002) Comprehensive analysis of the acute toxicities induced by systemic administration of cationic lipid: Plasmid DNA complexes in mice. Hum Gene Ther 11:2493–2513

    Google Scholar 

  72. Chollet P, Favrot MC, Hurbin A et al (2002) Side-effects of a systemic injection of linear polyethylenimine-DNA complexes. J Gene Med 4:84–91

    Google Scholar 

  73. Nishiyama N, Kataoka K (2006) Nanostructured devices based on block copolymer assemblies for drug delivery: designing structures for enhanced drug function. Adv Polym Sci 193:67–101

    CAS  Google Scholar 

  74. Akiyoshi K, Kobayashi S, Shichibe S et al (1998) Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier of protein drugs: Complexation and stabilization of insulin. J Control Release 54:313–320

    CAS  Google Scholar 

  75. Jung SW, Jeong Y, Kim SH (2003) Characterization of hydrophobized pullulan with various hydrophobicities. Int J Pharm 254:109–121

    CAS  Google Scholar 

  76. Na K, Park KH, Kim SW et al (2000) Self-assembled hydrogel nanoparticles from curdlan derivatives: characterization, anti-cancer drug release and interaction with a hepatoma cell line (HepG2). J Control Release 69:225–236

    CAS  Google Scholar 

  77. Gref R, Rodrigues J, Couvreur P (2002) Polysaccharides grafted with polyesters: novel amphiphilic copolymers for biomedical applications. Macromolecules 35:9861–9867

    CAS  Google Scholar 

  78. Leonard M, Boisseson MRD, Hubert P et al (2004) Hydrophobically modified alginate hydrogels as protein carriers with specific controlled release properties. J Control Release 98:395–405

    CAS  Google Scholar 

  79. Park JH, Kwona S, Nam JO et al (2004) Self-assembled nanoparticles based on glycol chitosan bearing 5h-cholanic acid for RGD peptide delivery. J Control Release 95:579–588

    CAS  Google Scholar 

  80. Akiyoshi K, Deguchi S, Moriguchi N et al (1993) Self-aggregates of hydrophobized polysaccharides in water. Formation and characteristics of nanoparticles. Macromolecules 26:3062–3068

    CAS  Google Scholar 

  81. Hsieh CY, Tsai SP, Wang DM et al (2005) Preparation of γ-PGA/chitosan composite tissue engineering matrices. Biomaterials 26:5617–5623

    CAS  Google Scholar 

  82. Kang HS, Park SH, Lee YG et al (2007) Polyelectrolyte complex hydrogel composed of chitosan and poly(γ-glutamic acid) for biological application: Preparation, physical properties, and cytocompatibility. J Appl Polym Sci 103:386–394

    CAS  Google Scholar 

  83. Kim YH, Gihm SH, Park CR et al (2001) Structural characteristics of size-controlled self-aggregates of deoxycholic acid-modified chitosan and their application as a DNA delivery carrier. Bioconjug Chem 12:932–938

    Google Scholar 

  84. Lee KY, Jo WH, Kwon IC et al (1998) Structural determination and interior polarity of self-aggregates prepared from deoxycholic acid-modified chitosan in water. Macromolecules 31:378–383

    CAS  Google Scholar 

  85. Kida T, Inoue K, Akagi T et al (2007) Preparation of novel polysaccharide nanoparticles by the self-assembly of amphiphilic pectins and their protein-encapsulation ability. Chem Lett 36:940–941

    CAS  Google Scholar 

  86. Muller M, Reihs T, Ouyang W (2005) Needlelike and spherical polyelectrolyte complex nanoparticles of poly(L-lysine) and copolymers of maleic acid. Langmuir 21:465–469

    CAS  Google Scholar 

  87. Hartig SM, Greene RR, DasGupta J et al (2007) Multifunctional nanoparticulate polyelectrolyte complexes. Pharm Res 24:2353–2369

    CAS  Google Scholar 

  88. Lin YH, Chung CK, Chen CT et al (2005) Preparation of nanoparticles composed of chitosan/poly-γ-glutamic acid and evaluation of their permeability through Caco-2 cells. Biomacromolecules 6:1104–1112

    CAS  Google Scholar 

  89. Hajdu I, Bodnar M, Filipcsei G et al (2009) Nanoparticles prepared by self-assembly of chitosan and poly-γ-glutamic acid. Colloid Polym Sci 286:343–350

    Google Scholar 

  90. Lin YH, Sonaje K, Lin KM et al (2008) Multi-ion-crosslinked nanoparticles with pH-responsive characteristics for oral delivery of protein drugs. J Control Release 132:141–149

    CAS  Google Scholar 

  91. Akagi T, Watanabe K, Kim H et al (2010) Stabilization of polyion complex nanoparticles composed of poly(amino acid) using hydrophobic interactions. Langmuir 26:2406–2413

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  93. Mundargi RC, Babu VR, Rangaswamy V et al (2008) Nano/micro technologies for delivering macromolecular therapeutics using poly(D, L-lactide-co-glycolide) and its derivatives. J Control Release 125:193–209

    CAS  Google Scholar 

  94. Sah H (1999) Stabilization of proteins against methylene chloride/water interface induced denaturation and aggregation. J Control Release 58:143–151

    CAS  Google Scholar 

  95. Panyam J, Dali MM, Sahoo SK et al (2003) Polymer degradation and in vitro release of a model protein from poly(D, L-lactide-co-glycolide) nano- and microparticles. J Control Release 92:173–187

    CAS  Google Scholar 

  96. Akagi T, Kaneko T, Kida T et al (2005) Preparation and characterization of biodegradable nanoparticles based on poly(γ-glutamic acid) with L-phenylalanine as a protein carrier. J Control Release 108:226–236

    CAS  Google Scholar 

  97. Akagi T, Kaneko T, Kida T et al (2006) Multifunctional conjugation of proteins on/into core-shell type nanoparticles prepared by amphiphilic poly(γ-glutamic acid). J Biomater Sci Polym Ed 17:875–892

    CAS  Google Scholar 

  98. Portilla-Arias JA, Camargo B, Garcia-Alvarez M et al (2009) Nanoparticles made of microbial poly(γ-glutamate)s for encapsulation and delivery of drugs and proteins. J Biomater Sci Polym Ed 20:1065–1079

    CAS  Google Scholar 

  99. O’Hagan DT (1998) Recent advances in immunological adjuvants: the development of particulate antigen delivery systems. Exp Opin Invest Drugs 7:349–359

    Google Scholar 

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

    CAS  Google Scholar 

  101. Shen H, Ackerman AL, Cody V et al (2006) Enhanced and prolonged cross-presentation following endosomal escape of exogenous antigens encapsulated in biodegradable nanoparticles. Immunology 117:78–88

    CAS  Google Scholar 

  102. Uto T, Wang X, Sato K et al (2007) Targeting of antigen to dendritic cells with poly(γ-glutamic acid) nanoparticles induce antigen-specific humoral and cellular immunity. J Immunol 178:2979–2986

    CAS  Google Scholar 

  103. Uto T, Akagi T, Hamasaki T et al (2009) Modulation of innate and adaptive immunity by biodegradable nanoparticles. Immunol Lett 125:46–52

    CAS  Google Scholar 

  104. Akagi T, Kim H, Akashi M (2010) pH-dependent disruption of erythrocyte membrane by amphiphilic poly(amino acid) nanoparticles. J Biomater Sci Polym Edn 21:315–328

    CAS  Google Scholar 

  105. Lutsiak ME, Robinson DR, Coester C et al (2002) Analysis of poly(D, L-lactic-co-glycolic acid) nanosphere uptake by human dendritic cells and macrophages in vitro. Pharm Res 19:1480–1487

    CAS  Google Scholar 

  106. Elamanchili P, Diwan M, Cao M et al (2004) Characterization of poly(D, L-lactic-co-glycolic acid) based nanoparticulate system for enhanced delivery of antigens to dendritic cells. Vaccine 22:2406–2412

    CAS  Google Scholar 

  107. Copland MJ, Baird MA, Rades T et al (2003) Liposomal delivery of antigen to human dendritic cells. Vaccine 21:883–890

    CAS  Google Scholar 

  108. Cohen JA, Beaudette TT, Tseng WW et al (2009) T-cell activation by antigen-loaded pH-sensitive hydrogel particles in vivo: the effect of particle size. Bioconjug Chem 20:111–119

    CAS  Google Scholar 

  109. Champion JA, Mitragotri S (2006) Role of target geometry in phagocytosis. Proc Natl Acad Sci USA 103:4930–4934

    CAS  Google Scholar 

  110. Champion JA, Mitragotri S (2009) Shape induced inhibition of phagocytosis of polymer particles. Pharm Res 26:244–249

    CAS  Google Scholar 

  111. Reddy ST, Swartz MA, Hubbell JA (2006) Targeting dendritic cells with biomaterials: developing the next generation of vaccines. Trends Immunol 27:573–579

    CAS  Google Scholar 

  112. Jones KS (2008) Biomaterials as vaccine adjuvants. Biotechnol Prog 24:807–814

    CAS  Google Scholar 

  113. Babensee JE (2007) Interaction of dendritic cells with biomaterials. Semin Immunol 20:101–108

    Google Scholar 

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

    CAS  Google Scholar 

  115. Black M, Trent A, Tirrell M et al (2010) Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists. Expert Rev Vaccines 9:157–173

    CAS  Google Scholar 

  116. Kim H, Uto T, Akag T et al (2010) Amphiphilic poly(amino acid) nanoparticles induce size-dependent dendritic cell maturation. Adv Funct Mater 20:3925–3931

    CAS  Google Scholar 

  117. Akagi T, Shima F, Akashi M (2011) Intracellular degradation and distribution of protein-encapsulated amphiphilic poly(amino acid) nanoparticles. Biomaterials 32:4959–4967

    CAS  Google Scholar 

  118. Kim TW, Lee TY, Bae HC et al (2007) Oral administration of high molecular mass poly-γ-glutamate induces NK cell-mediated antitumor immunity. J Immunol 179:775–780

    CAS  Google Scholar 

  119. Lee TY, Kim YH, Yoon SW et al (2009) Oral administration of poly-γ-glutamate induces TLR4- and dendritic cell-dependent antitumor effect. Cancer Immunol Immunother 58:1781–1794

    CAS  Google Scholar 

  120. Tamayo I, Irache JM, Mansilla C et al (2010) Poly(anhydride) nanoparticles act as active Th1 adjuvants through Toll-like receptor exploitation. Clin Vaccine Immunol 17:1356–1362

    CAS  Google Scholar 

  121. Yoshida M, Babensee JE (2004) Poly(lactic-co-glycolic acid) enhances maturation of human monocyte-derived dendritic cells. J Biomed Mater Res 71:45–54

    Google Scholar 

  122. Jilek S, Ulrich M, Merkle HP et al (2004) Composition and surface charge of DNA-loaded microparticles determine maturation and cytokine secretion in human dendritic cells. Pharm Res 21:1240–1247

    CAS  Google Scholar 

  123. Thiele L, Rothen-Rutishauser B, Jilek S et al (2001) Evaluation of particle uptake in human blood monocyte-derived cells in vitro. Does phagocytosis activity of dendritic cells measure up with macrophages? J Control Release 76:59–71

    CAS  Google Scholar 

  124. Matsusaki M, Larsson K, Akagi T et al (2005) Nanosphere induced gene expression in human dendritic cells. Nano Lett 5:2168–2173

    CAS  Google Scholar 

  125. Kwon YJ, Standley SM, Goh SL et al (2005) Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles. J Control Release 105:199–212

    CAS  Google Scholar 

  126. Sun H, Pollock KG, Brewer JM (2003) Analysis of the role of vaccine adjuvants in modulating dendritic cell activation and antigen presentation in vitro. Vaccine 21:849–855

    CAS  Google Scholar 

  127. Waeckerle-Men Y, Allmen EU, Gander B et al (2006) Encapsulation of proteins and peptides into biodegradable poly(D, L-lactide-co-glycolide) microspheres prolongs and enhances antigen presentation by human dendritic cells. Vaccine 24:1847–1857

    CAS  Google Scholar 

  128. Li SD, Huang L (2006) Gene therapy progress and prospects: non-viral gene therapy by systemic delivery. Gene Ther 13:1313–1319

    CAS  Google Scholar 

  129. Mann A, Richa R, Ganguli M (2008) DNA condensation by poly-L-lysine at the single molecule level: role of DNA concentration and polymer length. J Control Release 125:252–262

    CAS  Google Scholar 

  130. Lee PW, Peng SF, Su CJ et al (2008) The use of biodegradable polymeric nanoparticles in combination with a low-pressure gene gun for transdermal DNA delivery. Biomaterials 29:742–751

    CAS  Google Scholar 

  131. Peng SF, Yang MJ, Su CJ et al (2009) Effects of incorporation of poly(γ-glutamic acid) in chitosan/DNA complex nanoparticles on cellular uptake and transfection efficiency. Biomaterials 30:1797–1808

    CAS  Google Scholar 

  132. Kurosaki T, Kitahara T, Fumoto S et al (2009) Ternary complexes of pDNA, polyethylenimine, and gamma-polyglutamic acid for gene delivery systems. Biomaterials 30:2846–2853

    CAS  Google Scholar 

  133. Plank C, Zauner W, Wagner E (1998) Application of membrane-active peptides for drug and gene delivery across cellular membranes. Adv Drug Deliv Rev 34:21–35

    CAS  Google Scholar 

  134. Shai Y (1999) Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by α-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim Biophys Acta 1462:55–70

    CAS  Google Scholar 

  135. Yessine MA, Leroux JC (2004) Membrane-destabilizing polyanions: interaction with lipid bilayers and endosomal escape of biomacromolecules. Adv Drug Deliv Rev 56:999–1021

    CAS  Google Scholar 

  136. Chen R, Yue Z, Eccleston ME et al (2005) Modulation of cell membrane disruption by pH-responsive pseudo-peptides through grafting with hydrophilic side chains. J Control Release 108:63–72

    CAS  Google Scholar 

  137. Murthy N, Xu M, Schuck S et al (2003) A macromolecular delivery vehicle for protein-based vaccines: Acid-degradable protein-loaded microgels. Proc Natl Acad Sci USA 29:4995–5000

    Google Scholar 

  138. Standley SM, Kwon TJ, Murthy N et al (2004) Acid-degradable particles for protein-based vaccines: Enhanced survival rate for tumor-challenged mice using ovalbumin model. Bioconjug Chem 15:1281–1288

    CAS  Google Scholar 

  139. Hu Y, Litwin T, Nagaraja AR et al (2007) Cytosolic delivery of membrane-impermeable molecules in dendritic cells using pH-responsive core-shell nanoparticles. Nano Lett 7:3056–3064

    CAS  Google Scholar 

  140. Boussif O, Lezoualc'h F, Zanta MA et al (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo. Proc Natl Acad Sci USA 92:7297–7301

    CAS  Google Scholar 

  141. Murthy N, Robichaud JR, Tirrell DA et al (1999) The design and synthesis of polymers for eukaryotic membrane disruption. J Control Release 61:137–143

    CAS  Google Scholar 

  142. Jones RA, Cheung CY, Black FE et al (2003) Poly(2-alkylacrylic acid) polymers deliver molecules to the cytosol by pH-sensitive disruption of endosomal vesicles. Biochem J 372:65–75

    CAS  Google Scholar 

  143. Kusonwiriyawong C, van de Wetering P, Hubbell JA et al (2003) Evaluation of pH-dependent membrane-disruptive properties of poly(acrylic acid) derived polymers. Eur J Pharm Biopharm 56:237–246

    CAS  Google Scholar 

  144. Yessine MA, Meier C, Petereit HU et al (2006) On the role of methacrylic acid copolymers in the intracellular delivery of antisense oligonucleotides. Eur J Pharm Biopharm 63:1–10

    CAS  Google Scholar 

  145. Foster S, Duvall CL, Crownover EF et al (2010) Intracellular delivery of a protein antigen with an endosomal-releasing polymer enhances CD8 T-cell production and prophylactic vaccine efficacy. Bioconjug Chem 21:2205–2212

    CAS  Google Scholar 

  146. Yoshikawa T, Okada N, Oda A et al (2008) Development of amphiphilic γ-PGA-nanoparticle based tumor vaccine: potential of the nanoparticulate cytosolic protein delivery carrier. Biochem Biophys Res Commun 366:408–413

    CAS  Google Scholar 

  147. Panyam J, Zhou WZ, Prabha S et al (2002) Rapid endo-lysosomal escape of poly(dl-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB J 16:1217–1226

    CAS  Google Scholar 

  148. Uto T, Wang X, Akagi T et al (2009) Improvement of adaptive immunity by antigen-carrying biodegradable nanoparticles. Biochem Biophys Res Commun 379:600–604

    CAS  Google Scholar 

  149. Hamasaki T, Uto TA et al (2010) Modulation of gene expression related to Toll-like receptor signaling in dendritic cells by poly(γ-glutamic acid) nanoparticles. Clin Vaccine Immunol 17:748–756

    CAS  Google Scholar 

  150. Wang X, Uto T, Akagi T et al (2007) Induction of potent CD8+ T-cell responses by novel biodegradable nanoparticles carrying human immunodeficiency virus type 1 gp120. J Virol 81:10009–10016

    CAS  Google Scholar 

  151. Wang X, Uto T, Akagi T et al (2008) Poly(γ-glutamic Acid) nanoparticles as an efficient antigen delivery and adjuvant system: potential for an anti-AIDS vaccine. J Med Virol 80:11–19

    CAS  Google Scholar 

  152. Okamoto S, Yoshii H, Akagi T et al (2007) Influenza hemagglutinin vaccine with poly(γ-glutamic acid) nanoparticles enhances the protection against influenza virus infection through both humoral and cell-mediated immunity. Vaccine 25:8270–8278

    CAS  Google Scholar 

  153. Okamoto S, Matsuura M, Akagi T et al (2009) Poly(γ-glutamic acid) nano-particles combined with mucosal influenza virus hemagglutinin vaccine protects against influenza virus infection in mice. Vaccine 27:5896–5905

    CAS  Google Scholar 

  154. Okamoto S, Yoshii H, Ishikawa T et al (2008) Single dose of inactivated Japanese encephalitis vaccine with poly(γ-glutamic acid) nanoparticles provides effective protection from Japanese encephalitis virus. Vaccine 26:589–594

    CAS  Google Scholar 

  155. Matsuo K, Yoshikawa T, Oda A et al (2007) Efficient generation of antigen-specific cellular immunity by vaccination with poly(γ-glutamic acid) nanoparticles entrapping endoplasmic reticulum-targeted peptides. Biochem Biophys Res Commun 362:1069–1072

    CAS  Google Scholar 

  156. Yoshikawa T, Okada N, Oda A et al (2008) Nanoparticles built by self-assembly of am phiphilic poly(γ-glutamic acid) can deliver antigens to antigen-presenting cells with high efficiency: A new tumor-vaccine carrier for eliciting effector T cells. Vaccine 26:1303–1313

    CAS  Google Scholar 

  157. Yamaguchi S, Tatsumi T, Takehara T et al (2010) EphA2-derived peptide vaccine with amphiphilic poly(gamma-glutamic acid) nanoparticles elicits an anti-tumor effect against mouse liver tumor. Cancer Immunol Immunother 59:759–767

    CAS  Google Scholar 

  158. Akagi T, Higashi M, Kaneko T et al (2005) In vitro enzymatic degradation of nanoparticles prepared from hydrophobically-modified poly(γ-glutamic acid). Macromol Biosci 5:598–602

    CAS  Google Scholar 

  159. Akagi T, Higashi M, Kaneko T et al (2006) Hydrolytic and enzymatic degradation of nanoparticles based on amphiphilic poly(γ-glutamic acid)-graft-L-phenylalanine copolymer. Biomacromolecules 7:297–303

    CAS  Google Scholar 

  160. Akagi T, Baba M, Akashi M (2007) Preparation of nanoparticles by the self-organization of polymers consisting of hydrophobic and hydrophilic segments: potential applications. Polymer 48:6729–6747

    CAS  Google Scholar 

  161. Kim H, Akagi T, Akashi M (2010) Preparation of CpG ODN-encapsulated anionic poly(amino acid) nanoparticles for gene delivery. Chem Lett 39:278–279

    CAS  Google Scholar 

  162. Raghuvanshi RS, Katare YK, Lalwani K et al (2002) Improved immune response from biodegradable polymer particles entrapping tetanus toxoid by use of different immunization protocol and adjuvants. Int J Pharm 245:109–121

    CAS  Google Scholar 

  163. Ataman-Onal Y, Munier S, Ganée A et al (2006) Surfactant-free anionic PLA nanoparticles coated with HIV-1 p24 protein induced enhanced cellular and humoral immune responses in various animal models. J Control Release 112:175–185

    Google Scholar 

  164. Hamdy S, Elamanchili P, Alshamsan A et al (2007) Enhanced antigen-specific primary CD4+ and CD8+ responses by codelivery of ovalbumin and toll-like receptor ligand monophosphoryl lipid A in poly(D, L-lactic-co-glycolic acid) nanoparticles. J Biomed Mater Res A 81:652–662

    Google Scholar 

  165. Solbrig CM, Saucier-Sawyer JK, Cody V et al (2007) Polymer nanoparticles for immunotherapy from encapsulated tumor-associated antigens and whole tumor cells. Mol Pharm 4:47–57

    CAS  Google Scholar 

  166. Wendorf J, Chesko J, Kazzaz J et al (2008) A comparison of anionic nanoparticles and microparticles as vaccine delivery systems. Hum Vaccin 4:44–49

    CAS  Google Scholar 

  167. Nayak B, Panda AK, Ray P et al (2009) Formulation, characterization and evaluation of rotavirus encapsulated PLA and PLGA particles for oral vaccination. J Microencapsul 26:154–165

    CAS  Google Scholar 

  168. Hamdy S, Molavi O, Ma Z et al (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 26:5046–5057

    CAS  Google Scholar 

  169. Caputo A, Sparnacci K, Ensoli B et al (2008) Functional polymeric nano/microparticles for surface adsorption and delivery of protein and DNA vaccines. Curr Drug Deliv 5:230–242

    CAS  Google Scholar 

  170. Slütter B, Plapied L, Fievez V et al (2009) Mechanistic study of the adjuvant effect of biodegradable nanoparticles in mucosal vaccination. J Control Release 138:113–121

    Google Scholar 

  171. Gutierro I, Hernández RM, Igartua M et al (2002) Size dependent immune response after subcutaneous, oral and intranasal administration of BSA loaded nanospheres. Vaccine 21:67–77

    CAS  Google Scholar 

  172. Chong CS, Cao M, Wong WW et al (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

    CAS  Google Scholar 

  173. Reddy ST, Rehor A, Schmoekel HG (2006) In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles. J Control Release 112:26–34

    CAS  Google Scholar 

  174. Reddy ST, Van Der Vlies AJ, Simeoni E et al (2007) Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nat Biotechnol 25:1159–1164

    CAS  Google Scholar 

  175. Fifis T, Gamvrellis A, Crimeen-Irwin B et al (2004) Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors. J Immunol 173:3148–3154

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mitsuru Akashi .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Akagi, T., Baba, M., Akashi, M. (2011). Biodegradable Nanoparticles as Vaccine Adjuvants and Delivery Systems: Regulation of Immune Responses by Nanoparticle-Based Vaccine. In: Kunugi, S., Yamaoka, T. (eds) Polymers in Nanomedicine. Advances in Polymer Science, vol 247. Springer, Berlin, Heidelberg. https://doi.org/10.1007/12_2011_150

Download citation

Publish with us

Policies and ethics