Mixed pH-Sensitive Polymeric Micelles for Combination Drug Delivery

Purpose To prepare mixed polymeric micelles that can carry two different drugs, doxorubicin (DOX) and 17-hydroxyethylamino-17-demethoxygeldanamycin (GDM-OH), for combination cancer chemotherapy. Methods The pH-sensitive micelles were prepared from poly(ethylene glycol)-poly(aspartate hydrazide) bloc...

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Bibliographic Details
Published in:Pharmaceutical research 2010-11, Vol.27 (11), p.2421-2432
Main Authors: Bae, Younsoo, Alani, Adam W. G, Rockich, Nicole C, Lai, T. S. Z. Chung, Kwon, Glen S
Format: Article
Language:English
Subjects:
Aqueous chemistry
Biochemistry
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Blotting, Western
Cell Line, Tumor
Chemotherapy
combination chemotherapy
Comparative studies
Drug Carriers
drug delivery
General pharmacology
Humans
Hydrogen-Ion Concentration
Magnetic Resonance Spectroscopy
Medical Law
Medical sciences
Micelles
mixed micelles
pH-controlled release
Pharmaceutical technology. Pharmaceutical industry
Pharmacology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Pharmacy
polymeric micelles
Polymers
Research Paper
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Summary:Purpose To prepare mixed polymeric micelles that can carry two different drugs, doxorubicin (DOX) and 17-hydroxyethylamino-17-demethoxygeldanamycin (GDM-OH), for combination cancer chemotherapy. Methods The pH-sensitive micelles were prepared from poly(ethylene glycol)-poly(aspartate hydrazide) block copolymers to which either DOX or GDM-OH is conjugated through acid-labile hydrazone bond (individual micelles). Mixed micelles were formed not only by simply mixing two different individual micelles in aqueous solutions (aqueous mixed micelles) but also by evaporating organic solvents from the organic/aqueous mixed solvents in which two block copolymers possessing different drugs were dissolved homogeneously (organic mixed micelles). Particle size measurements, pH-dependent drug release tests, cytotoxicity assays and western blot analysis were subsequently conducted. Results Individual and aqueous/organic mixed micelles showed clinically relevant particle size (
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-010-0234-3