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 6months) 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.
Sanson
Charles
C
Université de Bordeaux, ENSCBP, 16 avenue Pey Berland, 33607 Pessac Cedex, France.
Schatz
Christophe
C
Le Meins
Jean-François
JF
Soum
Alain
A
Thévenot
Julie
J
Garanger
Elisabeth
E
Lecommandoux
Sébastien
S
D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004146:Dioxanes / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D036103:Nanotechnology; D011099:Polyglutamic Acid / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004146:Dioxanes; D004337:Drug Carriers; D011108:Polymers; D011099:Polyglutamic Acid; C059299:polytrimethylene carbonate; D004317:Doxorubicin