Direct, controlled synthesis of the nonimmunogenic, hydrophilic polymer, poly(N-(2-hydroxypropyl)methacrylamide) via RAFT in aqueous media

Poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) is a nonimmunogenic, neutral-hydrophilic polymer currently employed in the delivery of anticancer drugs. Herein, we report conditions that facilitate the direct, controlled RAFT polymerization of HPMA in aqueous media. We demonstrate that the use of 4-cyanopentanoic acid dithiobenzoate and 4,4'-azobis(4-cyanopentanoic acid) as the chain transfer agent (CTA) and initiating species, respectively, in the presence of an acetic acid buffer solution at 70 degrees C is a suitable condition leading to controlled polymerization. The "living" nature of these polymerizations is demonstrated via chain-extension of an HPMA macroCTA to yield the corresponding poly(HPMA-b-HPMA) "homopolymer".