Maria Torres

The overall goal of our research is to design novel vaccine biodegradable systems based on polyanhydrides for the stabilization and sustained release of peptides and proteins. Polyanhydrides, which are surface erodible water-labile polymers, have shown excellent performance as drug carriers. Their hydrophobic nature prevents water penetration into the bulk, thus eliminating water-induced covalent aggregation of proteins. However, protein inactivation by non-covalent aggregation due to hydrophobic interactions remains an issue. Previous studies have indicated that amphiphilic polymers offer a gentle environment for proteins. Our hypothesis is that incorporation of hydrophilic entities, such as oligomeric ethylene glycol, into anhydride monomers may prevent protein inactivation by both covalent and non-covalent aggregation. Accordingly, we have synthesized copolymers of the anhydrides, 1,6-bis(p-carboxyphenoxy)hexane (CPH) and 1,8-bis(p-carboxyphenoxy)-3, 6-dioxaoctane (CPTEG), which is a monomer containing oligomeric ethylene glycol moieties. It was found that the CPTEG:CPH system preserves the structural hierarchy of the encapsulated proteins. The ability to effect immune deviation and use the responses induced by the CPTEG:CPH system to elucidate and enhance the cellular and molecular mechanisms responsible for anti-tumor immunity will be elucidated. We have synthesized CPTEG:CPH polyanhydride nanospheres, which will be tested for activation of immune cells. Altogether, this research will provide novel insights into the mechanisms of adjuvanticity to enhance the appropriate immune responses.