DEVELOPMENT OF N-(2-HYDROXYPROPYL)METHACRYLAMIDE COPOLYMER CONJUGATES FOR DELIVERY OF CANCER-CHEMOTHERAPY

In recent years a series of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers have been synthesised containing antitumour agents, particularly doxorubicin (Dox) bound to the polymer carrier by peptidyl spacers designed for cleavage by lysosomal thiol-dependent proteases, enzymes known to show increased activity in metastatic tumours. Such conjugates display a broad range of antitumour activities against leukaemic, solid tumour and metastatic models, and recent experimentation has focussed on investigating further their mechanism of action. It is believed that drug conjugation leads to reduced toxicity, passive accumulation within solid tumours due to the enhanced permeability and retention effect and subsequent controlled drug release. All these factors contribute to the improved antitumour activity seen.