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.
Bibliographical noteFunding Information:
This research was supported by funding from the University of Otago . S.G. gratefully acknowledges the University of Otago and the National School of Pharmacy for the provision of a University of Otago Postgraduate Scholarship and a PhD stipend, respectively. Technical assistance from Liz Girvan at the Otago Centre for Electron Microscopy is also gratefully acknowledged.
- Immune response
- Particulate sustained release vaccine delivery system
- Silica nanoparticles
- Thermosensitive hydrogel
ASJC Scopus subject areas
- Pharmaceutical Science