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

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

Research output: Contribution to journalArticle

192 Scopus citations

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, 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.

Original languageEnglish (US)
Pages (from-to)294-300
Number of pages7
JournalJournal of Controlled Release
Volume140
Issue number3
DOIs
StatePublished - Dec 16 2009

Keywords

  • Combination drug therapy
  • Cremophor EL
  • Drug solubilization
  • Heat shock protein 90 inhibitor
  • Polymeric micelle

ASJC Scopus subject areas

  • Pharmaceutical Science

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