Synthesis of Aliphatic Polyanhydrides for Drug and Vaccine Delivery

Many vaccines require a cold chain and typically need multiple doses to sustain long-lived immune memory. These challenges, particularly in rural and low-income areas, make vaccines less accessible. Thus, there is a need to develop novel vaccine formulations. Polyanhydrides represent a class of biodegradable polymers that have been studied extensively as drug and vaccine carriers. This vaccine platform offers multiple benefits, such as tunable release kinetics and stability at room temperature. Previously, polyanhydride copolymers based on 1,6-bis(p-carboxyphenoxy)hexane (CPH) have been utilized successfully to stabilize proteins, provide sustained release of antigenic payloads, and induce protective immunity in pre-clinical models. This work aims to expand the library of diacids used to synthesize anhydride copolymers by specifically focusing on suberic acid (SubA).

SubA:CPH copolymers of different compositions were synthesized using melt polycondensation. To characterize these copolymers Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyze molecular weight, purity, and degree of polymerization. Differential scanning calorimetry was used to measure thermal properties, including the glass transition temperature and melting temperature. The glass transition temperature indicates the temperature at which a polymer may be processable into particles; altering the composition of the copolymers may affect this temperature. Additionally, due to their similar hydrophobic properties, SubA:CPH copolymers were compared with more traditional sebacic acid (SA):CPH copolymers. The ultimate goal of this work is to evaluate the ability of the SubA:CPH copolymers to maintain protein stability and provide sustained release kinetics (with model proteins initially), with a view toward future studies with clinically relevant proteins.