Skip to main content

Gels as Vaccine Delivery Systems

Part of the Advances in Delivery Science and Technology book series (ADST)

Abstract

While the major application of gels has historically been as delivery systems for small molecule and protein/peptide drugs, the benefits of gels as delivery vehicles are being increasingly translated to the field of subunit vaccine delivery. This chapter will present a summary of gel systems commonly employed to date in the delivery of subunit antigens, categorised according to mechanism of gelation and principal gelling component. Examples of preclinical and also clinical studies in which gels have been employed as delivery systems for vaccines will be given. Gels as bulk delivery systems will be focused on in this chapter; however, the reader’s attention is also drawn to the increasingly popular application of nanogels (nanosized polymeric gels) as vaccine delivery systems.

Keywords

  • Human Papilloma Virus
  • Tetanus Toxoid
  • Vaccine Delivery
  • Sorbitan Monostearate
  • Vaccine Delivery System

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-4939-1417-3_11
  • Chapter length: 18 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   129.00
Price excludes VAT (USA)
  • ISBN: 978-1-4939-1417-3
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   169.99
Price excludes VAT (USA)
Hardcover Book
USD   199.99
Price excludes VAT (USA)
Fig. 11.1
Fig. 11.2
Fig. 11.3

References

  • Agarwal P, Rupenthal ID (2013) Injectable implants for the sustained release of protein and peptide drugs. Drug Discov Today 18(7–8):337–349

    CAS  PubMed  CrossRef  Google Scholar 

  • Almdal K, Dyre J, Hvidt S, Kramer O (1993) Towards a phenomenological definition of the term ‘gel’. Polym Gels Networks 1(1):5–17

    CAS  CrossRef  Google Scholar 

  • Amidi M, Romeijn SG, Borchard G, Junginger HE, Hennink WE, Jiskoot W (2006) Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system. J Control Release 111(1–2):107–116

    CAS  PubMed  CrossRef  Google Scholar 

  • Berger J, Reist M, Chenite A, Felt-Baeyens O, Mayer JM, Gurny R (2005) Pseudo-thermosetting chitosan hydrogels for biomedical application. Int J Pharm 288(1):17–25

    CAS  PubMed  CrossRef  Google Scholar 

  • Brown W, Schillen K, Almgren M, Hvidt S, Bahadur P (1991) Micelle and gel formation in a poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer in water solution: dynamic and static light scattering and oscillatory shear measurements. J Phys Chem 95(4):1850–1858

    CAS  CrossRef  Google Scholar 

  • Bueter CL, Lee CK, Rathinam VAK, Healy GJ, Taron CH, Specht CA, Levitz SM (2011) Chitosan but not chitin activates the inflammasome by a mechanism dependent upon phagocytosis. J Biol Chem 286(41):35447–35455

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Cabana A, Aı̈t-Kadi A, Juhász J (1997) Study of the gelation process of polyethylene oxidea–polypropylene oxideb–polyethylene oxidea copolymer (Poloxamer 407) aqueous solutions. J Colloid Interface Sci 190(2):307–312

    CAS  PubMed  CrossRef  Google Scholar 

  • Chenite A, Chaput C, Wang D, Combes C, Buschmann MD, Hoemann CD, Leroux JC, Atkinson BL, Binette F, Selmani A (2000) Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials 21(21):2155–2161

    CAS  PubMed  CrossRef  Google Scholar 

  • Chenite A, Buschmann M, Wang D, Chaput C, Kandani N (2001) Rheological characterisation of thermogelling chitosan/glycerol-phosphate solutions. Carbohydr Polym 46(1):39–47

    CAS  CrossRef  Google Scholar 

  • Chitkara D, Shikanov A, Kumar N, Domb AJ (2006) Biodegradable injectable in situ depot-forming drug delivery systems. Macromol Biosci 6(12):977–990

    CAS  PubMed  CrossRef  Google Scholar 

  • Cho J, Heuzey M-C, Bégin A, Carreau PJ (2005) Physical gelation of chitosan in the presence of β-glycerophosphate: the effect of temperature. Biomacromolecules 6(6):3267–3275

    CAS  PubMed  CrossRef  Google Scholar 

  • Christie RJ, Findley DJ, Dunfee M, Hansen RD, Olsen SC, Grainger DW (2006) Photopolymerized hydrogel carriers for live vaccine ballistic delivery. Vaccine 24(9):1462–1469

    CAS  PubMed  CrossRef  Google Scholar 

  • Chung HJ, Lee Y, Park TG (2008) Thermo-sensitive and biodegradable hydrogels based on stereocomplexed Pluronic multi-block copolymers for controlled protein delivery. J Control Release 127(1):22–30

    CAS  PubMed  CrossRef  Google Scholar 

  • Coeshott CM, Smithson SL, Verderber E, Samaniego A, Blonder JM, Rosenthal GJ, Westerink MAJ (2004) Pluronic® F127-based systemic vaccine delivery systems. Vaccine 22(19):2396–2405

    CAS  PubMed  CrossRef  Google Scholar 

  • Çokçalışkan C, Özyörük F, Gürsoy RN, Alkan M, Günbeyaz M, Arca HÇ, Uzunlu E, Şenel S (2013) Chitosan-based systems for intranasal immunization against foot-and-mouth disease. Pharm Dev Technol. doi:10.3109/10837450.2013.763263:1-8

    PubMed  Google Scholar 

  • Cole DJ, Gattoni-Celli S, McClay EF, Metcalf JS, Brown JM, Nabavi N, Newton DA, Woolhiser CB, Wilson MC, Vournakis JN (1997) Characterization of a sustained-release delivery system for combined cytokine/peptide vaccination using a poly-N-acetyl glucosamine-based polymer matrix. Clin Cancer Res 3(6):867–873

    CAS  PubMed  Google Scholar 

  • Cranage MP, Fraser CA, Stevens Z, Huting J, Chang M, Jeffs SA, Seaman MS, Cope A, Cole T, Shattock RJ (2009) Repeated vaginal administration of trimeric HIV-1 clade C gp140 induces serum and mucosal antibody responses. Mucosal Immunol 3(1):57–68

    PubMed Central  PubMed  CrossRef  Google Scholar 

  • Cranage MP, Fraser CA, Cope A, McKay PF, Seaman MS, Cole T, Mahmoud AN, Hall J, Giles E, Voss G, Page M, Almond N, Shattock RJ (2011) Antibody responses after intravaginal immunisation with trimeric HIV-1CN54 clade C gp140 in Carbopol gel are augmented by systemic priming or boosting with an adjuvanted formulation. Vaccine 29(7):1421–1430

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Danforth HD, Lee EH, Martin A, Dekich M (1997) Evaluation of a gel-immunization technique used with two different Immucox vaccine formulations in battery and floor-pen trials with broiler chickens. Parasitol Res 83(5):445–451

    CAS  PubMed  CrossRef  Google Scholar 

  • Dasgupta T, Lee EH (2000) A gel delivery system for coccidiosis vaccine: uniformity of distribution of oocysts. Can Vet J 41(8):613–616

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dey AK, Burke B, Sun Y, Hartog K, Heeney JL, Montefiori D, Srivastava IK, Barnett SW (2012) Use of a polyanionic carbomer, Carbopol971P, in combination with MF59, improves antibody responses to HIV-1 envelope glycoprotein. Vaccine 30(17):2749–2759

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Dumortier G, Grossiord JL, Agnely F, Chaumeil JC (2006) A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm Res 23(12):2709–2728

    CAS  PubMed  CrossRef  Google Scholar 

  • Ellis RW (2001) Technologies for the design, discovery, formulation and administration of vaccines. Vaccine 19(17–19):2681–2687

    CAS  PubMed  CrossRef  Google Scholar 

  • Felt O, Einmahl S, Gurny R, Furrer P, Baeyens V (2002) Polymeric systems for ophthalmic drug delivery. In: Dumitriu S (ed) Polymeric biomaterials, revised and expanded, 2nd edn. Marcel Dekker, New York

    Google Scholar 

  • Ganguly S, Dash AK (2004) A novel in situ gel for sustained drug delivery and targeting. Int J Pharm 276(1–2):83–92

    CAS  PubMed  CrossRef  Google Scholar 

  • Gombotz WR, Wee SF (1998) Protein release from alginate matrices. Adv Drug Deliv Rev 31(3):267–285

    CAS  PubMed  CrossRef  Google Scholar 

  • Gong C-Y, Shi S, Peng X-Y, Kan B, Yang L, Huang M-J, Luo F, Zhao X, Wei Y-Q, Qian Z-Y (2009) Biodegradable thermosensitive injectable PEG-PCL-PEG hydrogel for bFGF antigen delivery to improve humoral immunity. Growth Factors 27(6):377–383

    CAS  PubMed  CrossRef  Google Scholar 

  • Gordon S, Saupe A, McBurney W, Rades T, Hook S (2008) Comparison of chitosan nanoparticles and chitosan hydrogels for vaccine delivery. J Pharm Pharmacol 60(12):1591–1600

    CAS  PubMed  CrossRef  Google Scholar 

  • Gordon S, Teichmann E, Young K, Finnie K, Rades T, Hook S (2010) In vitro and in vivo investigation of thermosensitive chitosan hydrogels containing silica nanoparticles for vaccine delivery. Eur J Pharm Sci 41(2):360–368

    CAS  PubMed  CrossRef  Google Scholar 

  • Gordon S, Young K, Wilson R, Rizwan S, Kemp R, Rades T, Hook S (2012) Chitosan hydrogels containing liposomes and cubosomes as particulate sustained release vaccine delivery systems. J Liposome Res 22(3):193–204

    CAS  PubMed  CrossRef  Google Scholar 

  • Günbeyaz M, Faraji A, Özkul A, Puralı N, Şenel S (2010) Chitosan based delivery systems for mucosal immunization against bovine herpesvirus 1 (BHV-1). Eur J Pharm Sci 41(3–4):531–545

    PubMed  CrossRef  Google Scholar 

  • Gupta P, Vermani K, Garg S (2002) Hydrogels: from controlled release to pH-responsive drug delivery. Drug Discov Today 7(10):569–579

    CAS  PubMed  CrossRef  Google Scholar 

  • Han I-K, Kim YB, Kang H-S, Sul D, Jung W-W, Cho HJ, Oh Y-K (2006) Thermosensitive and mucoadhesive delivery systems of mucosal vaccines. Methods 38(2):106–111

    CAS  PubMed  CrossRef  Google Scholar 

  • He C, Kim SW, Lee DS (2008) In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery. J Control Release 127(3):189–207

    CAS  PubMed  CrossRef  Google Scholar 

  • Hori Y, Winans AM, Huang CC, Horrigan EM, Irvine DJ (2008) Injectable dendritic cell-carrying alginate gels for immunization and immunotherapy. Biomaterials 29(27):3671–3682

    CAS  PubMed  CrossRef  Google Scholar 

  • Hvidt S, Joergensen EB, Brown W, Schillen K (1994) Micellization and gelation of aqueous solutions of a triblock copolymer studied by rheological techniques and scanning calorimetry. J Phys Chem 98(47):12320–12328

    CAS  CrossRef  Google Scholar 

  • Ishihara M, Obara K, Nakamura S, Fujita M, Masuoka K, Kanatani Y, Takase B, Hattori H, Morimoto Y, Ishihara M, Maehara T, Kikuchi M (2006) Chitosan hydrogel as a drug delivery carrier to control angiogenesis. J Artif Organs 9(1):8–16

    CAS  PubMed  CrossRef  Google Scholar 

  • Jeong B, Kim SW, Bae YH (2002) Thermosensitive sol–gel reversible hydrogels. Adv Drug Deliv Rev 54(1):37–51

    CAS  PubMed  CrossRef  Google Scholar 

  • Kabanov AV, Batrakova EV, Alakhov VY (2002) Pluronic® block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release 82(2–3):189–212

    CAS  PubMed  CrossRef  Google Scholar 

  • Kashyap N, Kumar N, Kumar MNVR (2005) Hydrogels for pharmaceutical and biomedical applications. Crit Rev Ther Drug Carrier Syst 22(2):107–150

    CAS  PubMed  CrossRef  Google Scholar 

  • Klouda L, Mikos AG (2008) Thermoresponsive hydrogels in biomedical applications. Eur J Pharm Biopharm 68(1):34–45

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Kojarunchitt T, Hook S (2012) Thermoresponsive chitosan and poloxamer 407 hydrogels for drug and vaccine delivery. In: Câmara FV, Ferreira LJ (eds) Hydrogels: synthesis, characterization and applications. Biochemistry research trends. Nova Biomedical, Waltham

    Google Scholar 

  • Kojarunchitt T, Hook S, Rizwan S, Rades T, Baldursdottir S (2011) Development and characterisation of modified poloxamer 407 thermoresponsive depot systems containing cubosomes. Int J Pharm 408(1–2):20–26

    CAS  PubMed  CrossRef  Google Scholar 

  • Krashias G, Simon A-K, Wegmann F, Kok W-L, Ho L-P, Stevens D, Skehel J, Heeney JL, Moghaddam AE, Sattentau QJ (2010) Potent adaptive immune responses induced against HIV-1 gp140 and influenza virus HA by a polyanionic carbomer. Vaccine 28(13):2482–2489

    CAS  PubMed  CrossRef  Google Scholar 

  • Kumar S, Himmelstein KJ (1995) Modification of in situ gelling behavior of carbopol solutions by hydroxypropyl methylcellulose. J Pharm Sci 84(3):344–348

    CAS  PubMed  CrossRef  Google Scholar 

  • Lewis DJ, Fraser CA, Mahmoud AN, Wiggins RC, Woodrow M, Cope A, Cai C, Giemza R, Jeffs SA, Manoussaka M, Cole T, Cranage MP, Shattock RJ, Lacey CJ (2011) Phase I randomised clinical trial of an HIV-1CN54, Clade C, trimeric envelope vaccine candidate delivered vaginally. PLoS One 6(9):e25165

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Li H, Willingham SB, Ting JP-Y, Re F (2008) Cutting edge: inflammasome activation by alum and alum’s adjuvant effect are mediated by NLRP3. J Immunol 181(1):17–21

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Lofthouse S (2002) Immunological aspects of controlled antigen delivery. Adv Drug Deliv Rev 54(6):863–870

    CAS  PubMed  CrossRef  Google Scholar 

  • Maitre N, Brown JM, Demcheva M, Kelley JR, Lockett MA, Vournakis J, Cole DJ (1999) Primary T-cell and activated macrophage response associated with tumor protection using peptide/poly-N-acetyl glucosamine vaccination. Clin Cancer Res 5(5):1173–1182

    CAS  PubMed  Google Scholar 

  • Mao J, Kondu S, Ji H-F, McShane MJ (2006) Study of the near-neutral pH-sensitivity of chitosan/gelatin hydrogels by turbidimetry and microcantilever deflection. Biotechnol Bioeng 95(3):333–341

    CAS  PubMed  CrossRef  Google Scholar 

  • Murdan S (2005) Organogels in drug delivery. Expert Opin Drug Deliv 2(3):489–505

    CAS  PubMed  CrossRef  Google Scholar 

  • Murdan S, Bvd B, Gregoriadis G, Florence AT (1999a) Water-in-sorbitan monostearate organogels (water-in-oil gels). J Pharm Sci 88(6):615–619

    CAS  PubMed  CrossRef  Google Scholar 

  • Murdan S, Gregoriadis G, Florence AT (1999b) Sorbitan monostearate/polysorbate 20 organogels containing niosomes: a delivery vehicle for antigens? Eur J Pharm Sci 8(3):177–185

    CAS  PubMed  CrossRef  Google Scholar 

  • Nguyen CL, Bui JT, Demcheva M, Vournakis JN, Cole DJ, Gillanders WE (2001) Sustained release of granulocyte-macrophage colony-stimulating factor from a modular peptide-based cancer vaccine alters vaccine microenvironment and enhances the antigen-specific T-cell response. J Immunother 24(5):420–429

    CAS  CrossRef  Google Scholar 

  • Oh Y-K, Park J-S, Yoon H, Kim C-K (2003) Enhanced mucosal and systemic immune responses to a vaginal vaccine coadministered with RANTES-expressing plasmid DNA using in situ-gelling mucoadhesive delivery system. Vaccine 21(17–18):1980–1988

    CAS  PubMed  CrossRef  Google Scholar 

  • Park J-S, Oh Y-K, Yoon H, Kim JM, Kim C-K (2002) In situ gelling and mucoadhesive polymer vehicles for controlled intranasal delivery of plasmid DNA. J Biomed Mater Res 59(1):144–151

    CAS  PubMed  CrossRef  Google Scholar 

  • Park J-S, Oh Y-K, Kang M-J, Kim C-K (2003) Enhanced mucosal and systemic immune responses following intravaginal immunization with human papillomavirus 16L1 virus-like particle vaccine in thermosensitive mucoadhesive delivery systems. J Med Virol 70(4):633–641

    PubMed  CrossRef  Google Scholar 

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

    CAS  PubMed  CrossRef  Google Scholar 

  • Porporatto C, Bianco ID, Riera CM, Correa SG (2003) Chitosan induces different l-arginine metabolic pathways in resting and inflammatory macrophages. Biochem Biophys Res Commun 304(2):266–272

    CAS  PubMed  CrossRef  Google Scholar 

  • Porporatto C, Bianco ID, Correa SG (2005) Local and systemic activity of the polysaccharide chitosan at lymphoid tissues after oral administration. J Leukoc Biol 78(1):62–69

    CAS  PubMed  CrossRef  Google Scholar 

  • Prego C, García M, Torres D, Alonso MJ (2005) Transmucosal macromolecular drug delivery. J Control Release 101(1–3):151–162

    CAS  PubMed  CrossRef  Google Scholar 

  • Qin C, Gao J, Wang L, Zeng L, Liu Y (2006) Safety evaluation of short-term exposure to chitooligomers from enzymic preparation. Food Chem Toxicol 44(6):855–861

    CAS  PubMed  CrossRef  Google Scholar 

  • Ruel-Gariépy E, Leroux J-C (2004) In situ-forming hydrogels—review of temperature-sensitive systems. Eur J Pharm Biopharm 58(2):409–426

    PubMed  CrossRef  Google Scholar 

  • Ruel-Gariépy E, Leclair G, Hildgen P, Gupta A, Leroux JC (2002) Thermosensitive chitosan-based hydrogel containing liposomes for the delivery of hydrophilic molecules. J Control Release 82(2–3):373–383

    PubMed  CrossRef  Google Scholar 

  • Salem ML, Demcheva M, Gillanders WE, Cole DJ, Vournakis JN (2010) Poly-N-acetyl glucosamine gel matrix as a non-viral delivery vector for DNA-based vaccination. Anticancer Res 30(10):3889–3894

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sood N, Nagpal S, Nanda S, Bhardwaj A, Mehta A (2013) An overview on stimuli responsive hydrogels as drug delivery system. J Control Release. doi:10.1016/j.jconrel.2013.02.023

    PubMed  Google Scholar 

  • Tecante A, del Carmen Núñez Santiago M (2012) Solution properties of κ-carrageenan and its interaction with other polysaccharides in aqueous media. In: De Vicente J (ed) Rheology. InTech, Croatias

    Google Scholar 

  • Tomihata K, Ikada Y (1997) In vitro and in vivo degradation of films of chitin and its deacetylated derivatives. Biomaterials 18(7):567–575

    CAS  PubMed  CrossRef  Google Scholar 

  • VandeVord PJ, Matthew HWT, DeSilva SP, Mayton L, Wu B, Wooley PH (2002) Evaluation of the biocompatibility of a chitosan scaffold in mice. J Biomed Mater Res 59(3):585–590

    CAS  PubMed  CrossRef  Google Scholar 

  • Velasquez LS, Shira S, Berta AN, Kilbourne J, Medi BM, Tizard I, Ni Y, Arntzen CJ, Herbst-Kralovetz MM (2011) Intranasal delivery of Norwalk virus-like particles formulated in an in situ gelling, dry powder vaccine. Vaccine 29(32):5221–5231

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Westerink MAJ, Smithson SL, Srivastava N, Blonder J, Coeshott C, Rosenthal GJ (2001) ProJuvant™ (Pluronic F127®/chitosan) enhances the immune response to intranasally administered tetanus toxoid. Vaccine 20(5–6):711–723

    CAS  PubMed  CrossRef  Google Scholar 

  • Winter HH, Chambon F (1986) Analysis of linear viscoelasticity of a crosslinking polymer at the gel point. J Rheol 30(2):367–382

    CAS  CrossRef  Google Scholar 

  • Wu QJ, Zhu XC, Xiao X, Wang P, Dk X, Gong CY, Wang YS, Yang L, Wei YQ (2011) A novel vaccine delivery system: Biodegradable nanoparticles in thermosensitive hydrogel. Growth Factors 29(6):290–297

    CAS  PubMed  CrossRef  Google Scholar 

  • Wu Q, Gong C, Shi S, Wang Y, Huang M, Yang L, Zhao X, Wei Y, Qian Z (2012a) Mannan loaded biodegradable and injectable thermosensitive PCL-PEG-PCL hydrogel for vaccine delivery. Soft Mater 10(4):472–486

    CAS  CrossRef  Google Scholar 

  • Wu Y, Wei W, Zhou M, Wang Y, Wu J, Ma G, Su Z (2012b) Thermal-sensitive hydrogel as adjuvant-free vaccine delivery system for H5N1 intranasal immunization. Biomaterials 33(7):2351–2360

    CAS  PubMed  CrossRef  Google Scholar 

  • Wu Y, Wu S, Hou L, Wei W, Zhou M, Su Z, Wu J, Chen W, Ma G (2012c) Novel thermal-sensitive hydrogel enhances both humoral and cell-mediated immune responses by intranasal vaccine delivery. Eur J Pharm Biopharm 81(3):486–497

    CAS  PubMed  CrossRef  Google Scholar 

  • Zhao Z, Leong KW (1996) Controlled delivery of antigens and adjuvants in vaccine development. J Pharm Sci 85(12):1261–1270

    CAS  PubMed  CrossRef  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sarah Gordon .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Gordon, S. (2015). Gels as Vaccine Delivery Systems. In: Foged, C., Rades, T., Perrie, Y., Hook, S. (eds) Subunit Vaccine Delivery. Advances in Delivery Science and Technology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1417-3_11

Download citation