Mechanochemical Solid-State Polymerization. VII. The Nature of Hydrolysis of Novel Polymeric Prodrugs Prepared by Mechanochemical Copolymerization.

Abstract

Hydrophilic polymeric prodrugs have been prepared by the mechanochemical copolymerization of methacryloyl derivatives of bioactive compounds with acrylamide, which is a hydrophilic conventional vinyl monomer. The polymeric prodrugs homogeneous in composition, since mechanochemical copolymerization is ideal copolymerization under the present experimental conditions. It is also shown that the polymeric prodrugs have a narrow molecular weight distribution.The alkaline hydrolysis of polymeric prodrugs prepared by mechanochemical copolymerization has been examined in a heterogeneous system. Though the degree of hydrolysis of polymeric prodrugs increases with increasing the content of hydrophilic monomer in the copolymer, there exists a limit to the degree of hydrolysis attainable due to the retardation by the carboxylic group produced as a side chain of the polymer hydrolyzate. The rate of hydrolysis depended largely on the structural feature of the polymer hydrolyzate; the use of carbamoyl derivatives of bioactive compounds is valuable for improving the nature of hydrolysis, since the amino group formed with the progress of hydrolysis does not cause any retardation of the nucleophilic reaction of the hydroxyl anion.