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

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-solub...

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Bibliographic Details
Published in:Journal of controlled release 2009-12, Vol.140 (3), p.294-300
Main Authors: Shin, Ho-Chul, Alani, Adam W.G., Rao, Deepa A., Rockich, Nicole C., Kwon, Glen S.
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - chemistry
Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics
Biological and medical sciences
Chemistry, Pharmaceutical
Chromatography, High Pressure Liquid
Combination drug therapy
Cremophor EL
Drug Carriers
Drug Delivery Systems
Drug Design
Drug solubilization
General pharmacology
Glycerol - analogs & derivatives
Half-Life
Heat shock protein 90 inhibitor
Light
Magnetic Resonance Spectroscopy
Medical sciences
Micelles
Nephelometry and Turbidimetry
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Polymeric micelle
Polymers
Rats
Scattering, Radiation
Solubility
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Summary: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. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2009.04.024