METHOD FOR THE PREPARATION OF POLYMERIC CONJUGATES OF DOXORUBICIN WITH PH- CONTROLLED RELEASE OF THE DRUG

摘要

A method for the preparation of polymeric conjugates of N-(2- hydroxypropyl)methacrylamide and a methacryloylaminoacylhydrazone of doxorubicin with pH-controlled release of the drug, comprising the following three steps of synthesis: a. preparation of a monomeric methacryloylaminoacylhydrazine, wherein the aminoacyl is derived from an amino acid or oligopeptide, by reaction of a methacryloyl halide with the respective peptide, amino acid, or a derivative thereof, and subsequent hydrazinolysis, b. synthesis of a polymeric precursor by direct copolymerization of N-(2- hydroxypropyl)methacrylamide with the methacryloylaminoacylhydrazine, and c. binding of doxorubicin to the polymeric precursor by reaction thereof with doxorubicin hydrochloride.