A simple method to achieve high doxorubicin loading in biodegradable polymersomes

Doxorubicin (Dox), an anthracycline anticancer drug, was successfully incorporated into block copolymer vesicles of poly(trimethylene carbonate)- b-poly( l-glutamic acid) (PTMC- b-PGA) by a solvent-displacement (nanoprecipitation) method. pH conditions were shown to have a strong influence on loading capacity and release profiles. Substantial drug loading (47% w/w) was achieved at pH 10.5. After pH neutralization, aqueous dispersions of drug-loaded vesicles were found stable for a prolonged period of time (at least 6 months) without vesicle disruption or drug precipitation. Dox-loaded vesicles exhibited in vitro pH and temperature-dependent drug release profiles: release kinetics fastened in acid conditions or by increasing temperature. These features strongly support the interest of developing PTMC- b-PGA polymersomes as carriers for the controlled delivery of Dox. Doxorubicin loading was optimized and quantitatively and spatially controlled in polymersomes, which had consequences on release kinetics and drug availability. [Display omitted]