Fariyal Ahmed

Polymersomes: A New Platform for Drug Targeting

Liposomes were first described in literature more than 30 years ago by Bangham (1). They have since been used widely in many fundamental studies of amphiphilic systems as well as in applications to extend and control the delivery of a broad variety of drugs (Fig. 1A). Thousands of publications, reviews, and monographs (e.g., (2)) now exist on liposomes. A handful of the documents have expressed ideas that emerge as the clearest backdrop for outlining the motivation, formation, properties, and compatibility of novel polymer-based vesicle platforms called “polymersomes” (3) (Fig. 1B).

Controlled release and stealthy circulation of polymersomes

The biocompatibility and controlled release profiles of polymersome were investigated. These hyperstable self-assembled block copolymers were injected into rats to elucidate in vivo circulation lifetimes, t-half. For these synthetic vesicles, t-half is 20-30 hours, which is comparable to stealth liposomes. Clearance appears to be primarily mediated by opsonization in spite of the heavily PEGylated brush arising from the hydrophilic fractions of all these block copolymers. Nonetheless, the t-half of these polymersomes compares well with any stealth liposome system. Therefore, novel controlled release polymersomes were prepared by blending the hydrolysable block copolymer poly (ethyleneoaide)-poly(lactic acid) (PEO-PLA) with the diblock copolymer poly(ethyleneoaide)-poly(butadiene) (PEO-PBD). The average time, t-release, for encapsulant release in vitro is obtained from exponential decays in the intact vesicle population and ranges from tens of hours to days or longer. Release kinetics showed minimal difference in plasma at 37/spl deg/C and the rate depends linearly on the mean molar ratio of PEO-PLA incorporated into the vesicle membrane. We propose a mechanism of membrane poration wherein partially hydrolyzed PLA chains congregate and achieve the desired spontaneous membrane curvature by forming a pore and rupturing the membrane, synonymous with detergent-mediated poration, release, and degradation. Emerging studies probe the encapsulant release dynamics in vivo of systems with t-release = t-half.