Protein release from dihydroxyacetone-based poly(carbonate ester) matrices

Abstract

The release of therapeutics from solid polymer matrices is an important field of study in the area of controlled release. Here we report on the hydrolytic degradation of directly compressed discs comprised of statistically random polycarbonate esters based on lactic acid and dihydroxyacetone. The controlled release of two model proteins, bovine serum albumin and lysozyme, was explored using two percentage loadings (5 and 10 wt.%). A first order release pattern and a trend for faster protein release with increasing dihydroxyacetone content were observed over a time period ranging from 2.5 to 70days. To analyze the effects of the internal polymer matrix environment on protein stability the enzymatic activity of released lysozyme was monitored. The results show a high level of enzyme activity for the polycarbonate ester ratios with more dihydroxyacetone in the backbone and at least 50% activity over the first month of release from the co-polymer ratios with more lactic acid in the backbone. Modeling of the release kinetics using the Korsmeyer–Peppas model showed a high correlation, indicating that the release of protein is a complex mechanism controlled by protein diffusion through, and erosion of, the co-polymer matrix. The outcomes show that these polycarbonate esters may be useful materials for extended controlled release of proteins.