ABSTRACT

Improved therapies for the treatment of life-threatening and chronic debilitating disease are urgently needed. Many seek to achieve more effective chemotherapy through the use of nanosized drug carriers-now being called ‘‘nanomedicines.’’ The technologies being explored include nanoparticles (1), polymer-coated liposomes (2), antibodies (3), and polymer therapeutics (4). As liposomes, antibodies (and immunoconjugates), and polyethyleneglycolylated-proteins (5) are all now

routinely used clinically, and an increasing number of polymer-drug conjugates have entered clinical development, the field of innovative drug delivery is at last coming of age. Whilst polymers play a pivotal role in most of these technologies, the phrase ‘‘polymer therapeutics’’ was specifically coined (6) to include polymeric drugs, polymer-drug conjugates, polymer-protein conjugates, polymeric micelles (to which drug is covalently bound), and those multi-component polyplexes being developed as non-viral vectors for intracytoplasmic delivery. The water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) conjugates described here are polymer therapeutics. From the industrial standpoint they are new chemical entities (NCEs) rather than conventional drug delivery systems or formulations which simply entrap, solubilize or control drug release without resorting to chemical conjugation. Since the 1970s an impressive literature has grown reporting the synthesis, characterization, solution, and biological properties of an ever-larger family of HPMA copolymer conjugates. These include polymer-drug conjugates (many also bearing targeting ligands), polymer-protein conjugates, water-soluble crosslinked polymer conjugates, ‘‘star-shaped’’ conjugates, and even vesicles entrapping HPMA copolymer conjugates (Fig. 1, Tables 1 and 2).