title: Multi-drug delivery to tumor cells via micellar nanocarriers.
abstract: The aim of this study was to develop micellar nanocarriers for concomitant delivery of paclitaxel and 17-allylamino-17-demethoxygeldanamycin (17-AAG) for cancer therapy. Paclitaxel and 17-AAG were simultaneously loaded into polymeric micelles by a solvent evaporation method. Two candidate nanocarrier constructs, polyethylene glycol-poly(D, L-lactic acid) (PEG-PLA) micelles and PEG-distearoylphosphatidylethanolamine/tocopheryl polyethylene glycol 1000 (PEG-DSPE/TPGS) mixed micelles, were assessed for the release kinetics of the loaded drugs. Compared to PEG-PLA micelles, entrapment of paclitaxel and 17-AAG into PEG-DSPE/TPGS mixed micelles resulted in significantly prolonged release half-lives. The simultaneous incorporation of paclitaxel and 17-AAG into PEG-DSPE/TPGS mixed micelles was confirmed by (1)H NMR analysis. Paclitaxel/17-AAG-loaded PEG-DSPE/TPGS mixed micelles were as effective in blocking the proliferation of human ovarian cancer SKOV-3 cells as the combined free drugs. PEG-DSPE/TPGS mixed micelles may provide a novel and advantageous delivery approach for paclitaxel/17-AAG combination therapy.
authors.affiliation: Cancer Nanomedicine Laboratory, Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USA.
authors.forename: Usha
authors.initials: U
authors.lastname: Katragadda
authors.forename: Quincy
authors.initials: Q
authors.lastname: Teng
authors.forename: Bindhu Madhavi
authors.initials: BM
authors.lastname: Rayaprolu
authors.forename: Thripthy
authors.initials: T
authors.lastname: Chandran
authors.forename: Chalet
authors.initials: C
authors.lastname: Tan
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D016227:Benzoquinones / Q000008:administration & dosage; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D016503:Drug Delivery Systems; D005260:Female; D006207:Half-Life; D006801:Humans; D047029:Lactams, Macrocyclic / Q000008:administration & dosage; D008823:Micelles; D053758:Nanoparticles; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols / Q000737:chemistry; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D016227:Benzoquinones; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004338:Drug Combinations; D047029:Lactams, Macrocyclic; D008823:Micelles; D010714:Phosphatidylethanolamines; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D014810:Vitamin E; D011092:Polyethylene Glycols; C112765:tanespimycin; C014225:tocophersolan; D017239:Paclitaxel