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-b–PLA micelles. Combinations of PTX/17-AAG, ETO/17-AAG, DCTX/17-AAG and PTX/ETO/17-AAG were also solubilized in PEG-b–PLA micelles. PEG-b–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 ofmg/mL and were stable for 24 h in the 2- and 3-drug combination PEG-b–PLAmicelles. The stability of the 2- and 3-drug combination PEG-b–PLA micelles was due to the presence of 17-AAG. In vitro, t1/2 values for 2- and 3-drug combination PEG-b–PLA micelles spanned 1–5 h. PEG-b–PLA micelles offer a promising alternative for combination drug therapy without formulation related side effects.