SYNTHESIS OF NOVEL HYDROLYTICALLY DEGRADABLE HYDROGELS FOR CONTROLLED DRUG-RELEASE

This paper describes synthesis of hydrolytically degradable gels based on N-(2-hydroxypropyl)-methacrylamide copolymers with high potential for use in the synthesis of new drug release systems. The first part deals with a study of the dependence between conditions of crosslinking copolymerization, the course of copolymerization and final properties of hydrogels thus formed. The second part is devoted to the study of hydrolytic degradation of hydrogels and in vitro studies of doxorubicin and polymer-doxorubicin conjugate release from hydrogel matrix. We have shown that the hydrogels under study were stable under acidic conditions (in buffers at pH 5 and lower) and hydrolytically degradable at physiological pH (7.4). Both drug forms, free doxorubicin and its conjugate with water-soluble polymeric drug carrier, can be released from the hydrogel matrix at a rate depending on the rate of drug diffusion from the hydrogel, or the rate of hydrogel degradation, or at a rate controlled by a combination of both processes. In all cases the hydrogel matrix was degraded and a hydrophilic water-soluble polymeric product was formed. Biological evaluation of drug-hydrogel systems described in this paper is under way.