Depot versus dispersal: biodegradable polymer vaccination effects of size and chemistry (46.17)

Abstract

Abstract Development of safe and efficacious vaccine regimen including delivery vehicles, routes, and adjuvants is paramount to public health and preventive medicine. This study evaluated the whole body distribution of unique, surface eroding polymers prepared from aliphatic sebacic acid (SA) and aromatic 1,6-bis(p-carboxyphenoxy)hexane (CPH). The inherent surface erosion kinetics permit development of a single dose vaccine based on tailored release kinetics of immunogen, adjuvanticity and sparing of protein dose, and sustained antigen presentation. Fabrication methods were used to create a size range (400 nm to 10 µm) of particles encapsulating LSS 640 fluorophore. These particles were used to evaluate in vivo distribution following intranasal (IN) or subcutaneous (SC) administration to mice. Using live animal imaging at multiple time points, fluorescent analysis at the injection and distal anatomical sites establish that microparticles distributed in a pattern consistent with a depot effect that was dependent upon the injection route. In contrast, nanoparticles distributed systemically regardless of route. Ex vivo analysis of excised tissues verified nanoparticle distribution to distal sites. The ability to assess the depot and dispersal effect of this novel delivery platform in real time consequent to the induction of an antibody response will provide insight into how size and polymer chemistry can be used therapeutically to effect targeting of a vaccine to desired immune tissues.