POLYMERIC DRUG-DELIVERY OF ENZYMATICALLY DEGRADABLE PENDANT AGENTS - PEPTIDYL-LINKED PROCAINAMIDE MODEL SYSTEM STUDIES

Biodegradable polymeric drug delivery systems have become increasingly important for sustained release indications when a lime-limited drug implant is required. A new methacrylic copolymer consisting of enzymat ically-cleavable oligopeptidyl procainamide as pendant side chains was synthesized in a series of three reactions. Using high performance li quid chromatography (HPLC) analysis, procainamide release was monitore d while incubating polymer specimens in the presence of a model enzyme , alpha-chymotrypsin, in a physiologic buffer at 37 degrees C. It was found that the new polymeric drug conjugate was insoluble in aqueous s olutions 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 i ncubation under physiologic conditions. However, in the presence of al pha-chymotrypsin, the procainamide side chains were gradually enzymati cally cleaved over 20 days, and the rate of hydrolysis could be contro lled by varying the enzymatic incubation conditions. The enzymatic rat e dependency of each formulation was dependent upon the comonomer rati o and the degree of crosslinking. These two factors influenced the acc essibility of the water-insoluble polymers to enzyme. It is concluded that procainamide release from an enzymatically degradable pendant-pep tide link can be achieved in an enzymatically controllable manner. (C) 1997 Elsevier Science B.V.