- Biodegradable polymeric drug delivery systems have become increasingly important for sustained release indications when a time-limited drug implant is required. A new methacrylic copolymer consisting of enzymatically-cleavable oligopeptidyl procainamide as pendant side chains was synthesized in a series of three reactions. Using high performance liquid chromatography (HPLC) analysis, procainamide release was monitored while incubating polymer specimens in the presence of a model enzyme, α-chymotrypsin, in a physiologic buffer at 37°C. It was found that the new polymeric drug conjugate was insoluble in aqueous solutions and it was relatively stable when not in the presence of the enzyme, releasing not more than 5 mg of drug/g polymer after 30 days incubation under physiologic conditions. However, in the presence of α-chymotrypsin, the procainamide side chains were gradually enzymatically cleaved over 20 days, and the rate of hydrolysis could be controlled by varying the enzymatic incubation conditions. The enzymatic rate dependency of each formulation was dependent upon the comonomer ratio and the degree of crosslinking. These two factors influenced the accessibility of the water-insoluble polymers to enzyme. It is concluded that procainamide release from an enzymatically degradable pendant-peptide link can be achieved in an enzymatically controllable manner.