Sterilization, storage stability and in vivo biocompatibility of poly(trimethylene carbonate)/poly(adipic anhydride) blends

Biodegradable blends of poly(trimethylene carbonate) (PTMC) and poly(adipic anhydride) (PAA) have been proven to be strong candidates for controlled d rug delivery polymers in vitro. We now report on the stability, sterilizabi lity and in vivo local tissue response of these matrices. Blend matrices we re sterilized by beta-radiation or ethylene oxide gas treatment, stored at different times and temperatures, and analyzed for changes in physicochemic al properties. Moisture uptake at different relative humidities and storage times was determined. Sterilization procedures induced hydrolysis of the m atrices. Ethylene oxide gas sterilization had a significantly more marked e ffect upon the matrix properties than radiation treatment. The onset of deg radation was reflected in a decrease of crystallinity and molecular weight along with a change of blend composition. A similar onset of matrix degrada tion was observed upon storage in air. The physicochemical properties of th e blends were well preserved upon storage under argon atmosphere. Biocompat ibility of PTMC/PAA implants was assessed in the anterior chamber of rabbit s eyes for 1 month. At selected post-operative time points, aqueous humor w as analyzed for white blood cells and the corneal thickness was measured. T he results suggest good biocompatability of PTMC-rich matrices, whereas fas t eroding PAA-rich matrices caused inflammatory responses, due to a burst r elease of degradation products. (C) 2000 Elsevier Science Ltd. All rights r eserved.