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.