| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1426046 | Journal of Controlled Release | 2009 | 7 Pages |
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 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-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.
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