Journal article
A 3-in-1 Polymeric Micelle Nanocontainer for Poorly Water-Soluble Drugs
Molecular pharmaceutics, Vol.8(4), pp.1257-1265
08/01/2011
DOI: 10.1021/mp2000549
PMCID: PMC4896148
PMID: 21630670
Abstract
Poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) micelles have a proven capacity for drug solubilization and have entered phase III clinical trials as a substitute for Cremophor EL in the delivery of paclitaxel in cancer therapy. PEG-b-PLA is less toxic than Cremophor EL, enabling a doubling of paclitaxel dose in clinical trials. We show that PEG-b-PLA micelles act as a 3-in-1 nanocontainer for paclitaxel, 17-allylamino-17-demethoxygeldanamycin (17-AAG), and rapamycin for multiple drug solubilization. 3-in-1 PEG-b-PLA micelles were ca. 40 nm in diameter; dissolved paclitaxel, 17-AAG, and rapamycin in water at 9.0 mg/mL; and were stable for 24 h at 25 degrees C. The half-life for in vitro drug release (t(1/2)) for 3-in-1 PEG-b-PLA micelles was 1-15 h under sink conditions and increased in the order of 17-AAG, paclitaxel, and rapamycin. The t(1/2) values correlated with log P-o/w, values, implicating a diffusion-controlled mechanism for drug release. The IC50 value of 3-in-1 PEG-b-PLA micelles for MCF-7 and 4T1 breast cancer cell lines was 114 +/- 10 and 25 +/- 1 nM, respectively; combination index (CI) analysis showed that 3-in-1 PEG-b-PLA micelles exert strong synergy in MCF-7 and 4T1 breast cancer cell lines. Notably, concurrent intravenous (iv) injection of paclitaxel, 17-AAG, and rapamycin using 3-in-1 PEG-b-PLA micelles was well-tolerated by FVB albino mice. Collectively, these results suggest that PEG-b-PLA micelles carrying paclitaxel, 17-AAG, and rapamycin will provide a simple yet safe and efficacious 3-in-1 nanomedicine for cancer therapy.
Details
- Title: Subtitle
- A 3-in-1 Polymeric Micelle Nanocontainer for Poorly Water-Soluble Drugs
- Creators
- Ho-Chul Shin - Univ Wisconsin, Sch Pharm, Div Pharmaceut Sci, Madison, WI 53705 USAAdam W. G. Alani - Oregon State UniversityHyunah Cho - University of Wisconsin–MadisonYounsoo Bae - University of KentuckyJill M. Kolesar - University of Wisconsin–MadisonGlen S. Kwon - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- Molecular pharmaceutics, Vol.8(4), pp.1257-1265
- Publisher
- Amer Chemical Soc
- DOI
- 10.1021/mp2000549
- PMID
- 21630670
- PMCID
- PMC4896148
- ISSN
- 1543-8384
- eISSN
- 1543-8392
- Number of pages
- 9
- Grant note
- R01 AI043346 / NIAID NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01AI043346 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Language
- English
- Date published
- 08/01/2011
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984696542402771
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