Biodegradable random copolypeptides of β-benzyl L-aspartate and γ-methyl L-glutamate for the controlled release of testosterone

The random copolypeptides of β-benzyl L -aspartate (β-Bz L -Asp) and γ-methyl L -glutamate (γ-Me L -Glu) were synthesized and implanted subcutaneously in rats. It was found that the resulting copolypeptides are degraded and also have good biocompatibility in vivo. On the basis of these results, poly(β-Bz L -Asp-co-γ-Me L -Glu) was tried to be used as a material for a drug delivery system. Copolypeptide-testosterone composites were prepared at a pressure of 200 kg/cm² in the presence of a slight amount of dichloroethane. The in vivo release rate of testosterone from copolypeptide-drug composites was about 5,5 times higher than that in vitro. The in vivo release rate remained relatively constant over a period of 90 days at 0,22 mg/day. The serum testosterone concentration in castrated rats was 0,40 ng/ml and the value went up to 6,8 ng/ml after the biodegradable copolypeptide-testosterone composite was implanted and was kept constant for the duration of test.