title: Paclitaxel nanocrystals for overcoming multidrug resistance in cancer.
abstract: Here we described a paclitaxel (PTX) nanocrystal formulation using d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) as the sole excipient for overcoming multidrug resistance (MDR), a key challenge in current cancer therapy. To the best of our knowledge, it is the first report on PTX nanocrystals which can reverse MDR. TPGS serves as a surfactant to stabilize the nanocrystals and a P-gp inhibitor to reverse MDR. The size and morphology of the nanocrystals were studied by transmission electron microscopy, and the crystalline structure was determined by powder X-ray diffraction. An in vitro drug release profile showed that the nanocrystals exhibited sustained release kinetics compared to Taxol, which is the clinical paclitaxel formulation. The cytotoxicity and antitumor efficacy in xenograft models were also investigated. It is demonstrated that PTX/TPGS nanocrystals have significant advantages over Taxol in achieving better therapeutic effect in Taxol-resistant cancer cells both in vitro and in vivo, which was also confirmed by apoptosis assays. We envision that further development of this type of nanocrystal will provide a novel strategy for drug delivery and multidrug resistance treatment.
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7360, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Leaf
authors.initials: L
authors.lastname: Huang
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004355:Drug Stability; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel