Journal
PHARMACEUTICAL RESEARCH
Volume 27, Issue 11, Pages 2421-2432Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-010-0234-3
Keywords
combination chemotherapy; drug delivery; mixed micelles; pH-controlled release; polymeric micelles
Funding
- National Institutes of Health [R01 AI-43346-08]
- Kentucky Lung Cancer Research Program
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To prepare mixed polymeric micelles that can carry two different drugs, doxorubicin (DOX) and 17-hydroxyethylamino-17-demethoxygeldanamycin (GDM-OH), for combination cancer chemotherapy. 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. Individual and aqueous/organic mixed micelles showed clinically relevant particle size (< 100 nm) and pH-dependent drug release patterns. Mixed polymer micelles suppress cancer cell growth effectively in a drug concentration, mixing method and schedule-dependent way. Combination chemotherapy using polymeric micelles seems to minimize a schedule-dependent change in combination drug efficacy in comparison to drug combination using DMSO formulations.
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