Polyanhydride Nanoparticle Platforms for the Prevention and Treatment of Streptococcus Pneumoniae Infections

Nanoparticles and microparticles made from polyanhydrides have been demonstrated to act effectively as vaccine adjuvants and drug delivery platforms. Amphiphilic polyanhydrides are excellent candidates for vaccine delivery because of their ability to: stabilize and protect fragile antigens; provide a sustained release of antigen; and modulate the immune response. These polymers have excellent biocompatibility yielding non-toxic, non-mutagenic degradation products. We have previously demonstrated the encapsulation and release of pneumococcal surface protein A (PspA), a surface protein of Streptococcus pneumoniae, from two polyanhydride chemistries based on sebacic acid (SA), 1,6-bis-(p-carboxyphenoxy)hexane (CPH) and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG). PspA is a choline-binding protein found on the surface of all pneumococcal strains and has been shown to be a protective antigen against S. pneumoniae. Our in vitro studies demonstrate the sustained release of stable, antigenic PspA and in in vivo studies, nanovaccine formulations containing PspA induced high antibody titers in immunized mice.

Polyanhydride nanoparticles have also previously been shown to be an effective delivery platform for antibiotics. Encapsulation of antibiotics into particles resulted in an increase in the local concentration of drug and prevented rapid clearance of the antibiotic after administration.  Additionally, particle persistence and sustained release of antibiotic (or antimicrobial agent) may obviate the need for a multiple-dose course of treatment. Together, these studies lay the groundwork for a polyanhydride nanoparticle-based combination treatment against S. pneumoniae that addresses both pre-exposure (i.e., prophylaxis) as well as post-exposure (i.e., therapeutics).