Literature DB >> 19409432

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

Ho-Chul Shin1, Adam W G Alani, Deepa A Rao, Nicole C Rockich, Glen S Kwon.   

Abstract

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, t(1/2) 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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Year:  2009        PMID: 19409432      PMCID: PMC2787857          DOI: 10.1016/j.jconrel.2009.04.024

Source DB:  PubMed          Journal:  J Control Release        ISSN: 0168-3659            Impact factor:   9.776


  37 in total

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