New Amphiphilic Polyanhydride Copolymers for Vaccine Delivery

Polyanhydride nanoparticle-based vaccines (i.e. nanovaccines) have been explored as next generation vaccines due to their adjuvant characteristics and ability to release encapsulated proteins over a long duration, allowing for the possibility of single-dose administration of poorly immunogenic proteins. These nanovaccines have been shown to enhance immune responses as evidenced by sustained antibody production, robust germinal center formation and the ability to enhance cytotoxic T cell responses.

Polyanhydride copolymers comprise of 1,6-bis(p-carboxyphenoxy) hexane (CPH), 1,8-bis (p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG), and sebacic acid (SA), with each of these monomers offering its own beneficial properties. In particular, nanoparticles with high CPTEG molar composition have demonstrated improved stability of secondary and tertiary structures of encapsulated proteins, and enhanced cellular internalization and persistence. SA-rich chemistries have also demonstrated enhanced cell internalization, and improved shelf stability of encapsulated proteins, likely due to their higher glass transition temperatures. However, copolymer chemistries consisting of CPTEG and SA have not been studied to date.

In this study, several different chemistries of CPTEG and SA copolymers were synthesized by melt condensation and their physical properties were evaluated. Polyanhydrides with glass transition temperatures higher than body temperature were synthesized into nanoparticles encapsulating ovalbumin, a model antigen. Particle size was determined via scanning electron microscopy and the stability of released ovalbumin was evaluated using circular dichroism and fluorescence spectroscopy. The final part of this study explored nanoparticle internalization in RAW 264.7 macrophages to compare how well the CPTEG:SA chemistries’ were internalized by the cells in comparison to the CPH:SA and CPTEG:CPH chemistries. The studies performed indicate that the CPTEG:SA copolymers are promising candidates for vaccine delivery.