title: Mixed pH-sensitive polymeric micelles for combination drug delivery.
abstract: OBJECTIVE
  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 (<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.
  
  
  CONCLUSIONS
  Combination chemotherapy using polymeric micelles seems to minimize a schedule-dependent change in combination drug efficacy in comparison to drug combination using DMSO formulations.
authors.affiliation: Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, Kentucky 40536-0596, USA. younsoo.bae@uky.edu
authors.forename: Younsoo
authors.initials: Y
authors.lastname: Bae
authors.forename: Adam W G
authors.initials: AW
authors.lastname: Alani
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Rockich
authors.forename: T S Z Chung
authors.initials: TS
authors.lastname: Lai
authors.forename: Glen S
authors.initials: GS
authors.lastname: Kwon
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D004337:Drug Carriers; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D011108:Polymers
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers