Novel degradable poly(anhydride-esters) for controlled drug release

Abstract

This project centers on the synthesis of novel poly(anhydride-esters), which are biodegradable polymers consisting of two salicylic acid molecules linked by carboxylic acid derivatives. Several poly(anhydride-esters) have already been synthesized (Erdmann et al., 1999) with demonstrated biocompatibility (Macedo, 1999) and degradative properties (Erdmann and Uhrich, 1999) desirable for controlled delivery of salicylic acid. However, their glass transition temperatures (T_g's) are several degrees below body temperature (37 ^oC), which limits the number of potential medical applications. The goal of our project is to develop poly(anhydride-esters) with T_g's higher than 37 ^oC. To achieve this goal, we performed multi-step syntheses of a series of polymers varying the linker structure between salicylic acid moieties. Linker molecules included derivatives of succinic acid, terephthalic acid, 4,4'-oxybis(benzoic acid), and 1,4-cyclohexanedicarboxylic acid. All monomers, oligomers and polymers were characterized by proton nuclear magnetic resonance spectroscopy (to verify chemical structure), gel permeation chromatography (to measure molecular weight and polydispersity index), and differential scanning calorimetry and thermal gravimetric analysis (to determine thermal properties). All four of the new polymeric materials had T_g's above 75 ^oC, markedly higher than the T_g's of the first generation of poly(anhydride-esters). Because the terephthalate-based polymer showed the highest degree of polymerization, it is our polymer of choice for future in vitro degradation studies in aqueous media.