In vitro and in vivo investigation of thermosensitive chitosan hydrogels containing silica nanoparticles for vaccine delivery

Eur J Pharm Sci. 2010 Oct 9;41(2):360-8. doi: 10.1016/j.ejps.2010.07.004. Epub 2010 Jul 13.

Abstract

In this work silica nanoparticles (SNP) containing the model antigen ovalbumin (OVA) were incorporated into a thermosensitive chitosan hydrogel, and the resulting formulation investigated for its potential to act as a particulate sustained release vaccine delivery system. OVA-loaded SNP and chitosan hydrogels containing OVA-loaded SNP were prepared and characterised in vitro, and examined for their ability to elicit OVA-specific immune responses in vivo. Optimised SNP were found to be approximately 300nm in size with a moderate level of heterogeneity, a highly negative zeta potential, and an entrapment efficiency of approximately 7%. A porous particulate structure was indicated both by electron microscopy and a rapid release of fluorescently-labelled OVA (FITC-OVA) from SNP. Following successful incorporation of SNP into chitosan hydrogels, the release of both soluble and SNP-associated antigen from gel systems was quantified. Approximately 16% of total protein was released in a particulate form over a 14-day period, while approximately 35% was released as soluble antigen. Gel-based systems containing SNP-associated or soluble antigen in the presence or absence of the adjuvant Quil A (QA) demonstrated an ability to stimulate both cell mediated and humoral immunity in vivo. Chitosan gels containing OVA-loaded SNP and the adjuvant QA showed a significantly greater ability to induce CD4(+) T cell proliferation than chitosan gel containing soluble OVA and QA, indicating the future promise for such a system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chitosan / chemistry*
  • Female
  • Hydrogels*
  • In Vitro Techniques
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron, Scanning
  • Nanoparticles*
  • Silicon Dioxide*
  • Vaccines / administration & dosage*

Substances

  • Hydrogels
  • Vaccines
  • Silicon Dioxide
  • Chitosan