Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble anticancer drugs

[摘要] Current clinical and preclinical anticancer formulations are limited by their use of toxic excipients and stability issues upon combining different drug formulations. We have found that poly(ethylene glycol)-block-poly(D,L lactic acid) (PEG-b-PLA) micelles can deliver multiple poorly water-soluble drugs at clinically relevant doses. Paclitaxel (PTX), etoposide (ETO), docetaxel (DCTX) and 17-allylamino-17-demethyoxygeldanamycin (17-AAG) were solubilized individually in PEG-6-PLA micelles. Combinations of PTX/17-AAG, ETO/17-AAG, DCTX/17-AAG and PTX/ETO/17-AAG were also solubilized in PEG-6-PLA micelles. PEG-6-PLA micelles were characterized in terms of drug loading, size, stability and drug release. All anticancer agents in all combinations were all solubilized at the level of mg/mL and were stable for 24 h in the 2- and 3-drug combination PEG-b-PLA micelles. The stability of the 2- and 3-drug combination PEG-6-PLA micelles was due to the presence of 17-AAG. In vitro, t(1/2) values for 2- and 3-drug combination PEG-b-PLA micelles spanned 1-5 h. PEG-6-PLA micelles offer a promising alternative for combination drug therapy without formulation related side effects. (C) 2009 Elsevier B.V. All rights reserved.

[发布日期] 2009-12-16

[效力级别]  Proceedings Paper

[关键词] Polymeric micelle;Drug solubilization;Combination drug therapy;Cremophor EL;Heat shock protein 90 inhibitor