title: A TPGS-incorporating nanoemulsion of paclitaxel circumvents drug resistance in breast cancer.
abstract: Paclitaxel resistance is usually developed in clinical chemotherapy, which remains a major obstacle for successful cancer treatment. Herein, we attempted to develop a TPGS incorporating nanoemulsion of paclitaxel (NE-PTX) to circumvent the drug resistance in breast cancer. NE-PTX was prepared by a self-assembly technique and the physicochemical properties were characterized. The efficacy of NE-PTX on overcoming paclitaxel resistance was measured by in vitro and in vivo evaluation. The measured results indicated that NE-PTX was nanometer-sized droplets with the mean diameter of 24.93±3.45 nm. The IC50 value of paclitaxel in resistant MCF-7/ADR cells was greatly reduced from 101.45 μg/mL to 5.39 μg/mL, which indicated that the paclitaxel resistance was effectively reduced by NE-PTX. The reversal of paclitaxel resistance could mainly ascribe to the significant inhibition of P-gp activity and enhancement of anti-cancer activity. Moreover, the tumor volume in resistant tumor xenograft model treated with NE-PTX was only 10.06% of that of paclitaxel solution group, and the tumor inhibitory rate of NE-PTX reached 93.84%, which effectively verified the efficacy of NE-PTX on treating paclitaxel resistance. Thereby, NE-PTX could provide an effective strategy for circumventing paclitaxel resistance in breast cancer.
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Bu
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: He
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: zwzhang0125@simm.ac.cn.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: ypli@simm.ac.cn.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004655:Emulsions; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D014810:Vitamin E / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D004655:Emulsions; D014810:Vitamin E; C014225:tocophersolan; D017239:Paclitaxel
keywords: Breast cancer; Multidrug resistance; Nanoemulsion; Paclitaxel; Self-assembly; TPGS