Preparation and investigation of cross-linked copolymers containing antitumour agents

Abstract

Polymers with anti-tumour activity were prepared by reactions of the iso-propyl ester of p-bis(2-chloroethyl) aminophenylalanine with free aldehyde, epoxide and hydroxyl groups within macroporous cross-linked copolymers of either divinylbenzene and methacrylaldehyde, or glycidyl methacrylate and ethylene dimethacrylate, or 2-hyroxyethyl methacrylate and ethylene dimethacrylate. For use as pharmacologically active compounds bonded on polymers, the chemical stability of the bond between these compounds and the polymer is of importance and for this reason an investigation was carried out on the course of the hydrolysis of azomethine compounds prepared hy reactions between free aldehyde groups in copolymers of divinylbenzene and methacrylaldehyde with the iso-propyl ester of p-bis(2-chloroethyl) aminophenylalanine. The highest initial rate of hydrolysis was observed at the highest proton concentration. The testing in vivo of antitumour activity of the isopropyl ester of p-bis(2-chloroethyl)-aminophenylalanine embedded within the cross-linked copolymer was carried out intraperitoneally on five experimental transplanted tumours.