In vitro and in vivo investigation of thermosensitive chitosan hydrogels containing silica nanoparticles for vaccine delivery.
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.
Gordon
Sarah
S
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Teichmann
Elena
E
Young
Katherine
K
Finnie
Kim
K
Rades
Thomas
T
Hook
Sarah
S
D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D005260:Female; D020100:Hydrogels; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D012822:Silicon Dioxide; D014612:Vaccines / Q000008:administration & dosage*
D020100:Hydrogels; D014612:Vaccines; D012822:Silicon Dioxide; D048271:Chitosan