title: Micelles of d-α-Tocopheryl Polyethylene Glycol 2000 Succinate (TPGS 2K) for Doxorubicin Delivery with Reversal of Multidrug Resistance.
abstract: The purpose of this study is to investigate the ability of doxorubicin (DOX)-loaded d-α-tocopheryl polyethylene glycol 2000 succinate (TPGS 2K) micelles to overcome MDR in breast cancer treatment. The DOX-loaded TPGS 2K micelles exhibited an average size of around 23 nm, a near neutral zeta potential of around 4 mv and high encapsulation efficiency (85.22 ± 1.89%). The TPGS 2K conjugate did not have significant influences on the reduction of mitochondrial membrane potential (MMP) and the depletion of intracellular ATP level of MCF-7/ADR cells but had an evident effect on the inhibition of Verapamil-induced P-gp ATPase activity. In vitro cell culture experiments demonstrated the DOX-loaded TPGS 2K micelles, resulting in higher cellular uptake and more significant cytotoxicity effect against MCF-7/MDR cells than the free DOX solution. Additionally, the in vivo imaging study revealed DiR-loaded TPGS 2K micelles distributed selectively in MCF-7/ADR tumor-bearing nude mice and had a sufficient residence time. In the anticancer efficacy test with MCF-7/ADR tumor bearing nude mice, the DOX-loaded TPGS 2K micelles displayed significantly higher antitumor activity compared with free DOX solution at the same DOX dosage but less toxicity evaluated by the change of body weight and histological examination. Therefore, this drug delivery micellar system based on TPGS 2K conjugates can serve as a potential nanomedicine for reversing MDR.
authors.affiliation: ‡Department of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China.
authors.forename: Tangna
authors.initials: T
authors.lastname: Hao
authors.affiliation: §Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.|∥School of Pharmacy, Medical College of Soochow University, Suzhou 215123, PR China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.affiliation: †School of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
authors.affiliation: †School of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: †School of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: †School of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Sun
authors.affiliation: †School of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: †School of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry; D013696:Temperature; D014018:Tissue Distribution; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D014810:Vitamin E; D011092:Polyethylene Glycols; D004317:Doxorubicin; C014225:tocophersolan
keywords: TPGS 2K; chemotherapy; doxorubicin; drug delivery; multidrug resistance; self-assembled micelles