pH-Sensitive degradable polymersomes for triggered release of anticancer drugs: a comparative study with micelles.

pH-Sensitive degradable polymersomes and micelles were prepared based on diblock copolymer of poly(ethylene glycol) (PEG) and an acid-labile polycarbonate, poly(2,4,6-trimethoxybenzylidenepentaerythritol carbonate) (PTMBPEC). Polymersomes of PEG(1.9k)-PTMBPEC(6k) revealed average sizes of 100-200 nm. The acetals of polymersomes, similar to those of PEG(5k)-PTMBPEC(5.8k) micelles, though stable at pH 7.4 were prone to fast hydrolysis at mildly acidic pH of 4.0 and 5.0, with half lives of 0.5 and 3d, respectively. The acetal hydrolysis resulted in significant size increase of polymersomes, to over 1000 nm in 24h at pH 4.0. Drug encapsulation studies revealed that polymersomes were able to simultaneously load paclitaxel (PTX, hydrophobic) and doxorubicin hydrochloride (DOX.HCl, hydrophilic), whereas micelles loaded PTX only. Notably, polymersomes showed lower drug loading efficiencies for PTX than micelles (30.0-37.7% versus 61.4-65.2%). The in vitro release studies demonstrated that release of PTX and DOX.HCl from polymersomes was highly pH-dependent, i.e. significantly faster drug release at mildly acidic pH of 4.0 and 5.0 compared to physiological pH. Furthermore, much higher release rates were observed for PTX release from the polymersomes compared to that from the micelles under otherwise the same conditions. These pH-sensitive nano-sized degradable polymersomes hold great promise for combination therapy for cancers. Copyright 2009 Elsevier B.V. All rights reserved.