Biodegradable Particles as Vaccine Delivery Systems: Size Matters
Journal Title: The AAPS Journal - Year 2013, Vol 15, Issue 1
Abstract
Poly(lactide-co-glycolide) (PLGA) particles have strong potential as antigen delivery systems. The size of PLGA particles used to vaccinate mice can affect the magnitude of the antigen-specific immune response stimulated. In this study, we fabricated and characterized 17 μm, 7 μm, 1 μm, and 300 nm PLGA particles coloaded with a model antigen ovalbumin (OVA) and CpG oligodeoxynucleotides (CpG ODN). PLGA particles demonstrated a size-dependent burst release followed by a more sustained release of encapsulated molecules. PLGA particles that were 300 nm in size showed the highest internalization by, and maximum activation of, dendritic cells. The systemic antigen-specific immune response to vaccination was measured after administration of two intraperitoneal injections, 7 days apart, of 100 μg OVA and 50 μg CpG ODN in C57BL/6 mice. In vivo studies showed that 300 nm sized PLGA particles generated the highest antigen-specific cytotoxic T cell responses by days  14 and 21. These mice also showed the highest IgG2a:IgG1 ratio of OVA-specific antibodies on day  28. This study suggests that the smaller the PLGA particle used to deliver antigen and adjuvants the stronger the antigen-specific cytotoxic T cell response generated.
Authors and Affiliations
Vijaya B. Joshi, Sean M. Geary, Aliasger K. Salem
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The online version of this article (doi:10.1208/s12248-014-9698-0) contains supplementary material, which is available to authorized users.
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