title: Novel designed polyoxyethylene nonionic surfactant with improved safety and efficiency for anticancer drug delivery.
abstract: In order to limit the adverse reactions caused by polysorbate 80 in Taxotere(®), a widely used formulation of docetaxel, a safe and effective nanocarrier for this drug has been developed based on micelles formed by a new class of well-defined polyoxyethylene sorbitol oleate (PSO) with sorbitol as the matrix in aqueous solution. The physicochemical properties of the amphiphilic surfactant and the resulting micelles can be easily fine-tuned by the homogeneous sorbitol matrix and pure oleic acid. Composition, critical micelle concentration, and entrapment efficiency were investigated by ultraviolet visible spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, fluorospectrophotometry, and high-performance liquid chromatography. In vitro and in vivo evaluation revealed that PSO had exceptionally low hemolysis and histamine release rates compared with commercial polysorbate 80. Moreover, the tumor targeting delivery of PSO was investigated by in vivo imaging in S180 tumor-bearing mice. The results suggest that this novel delivery system, PSO, provides an acceptable alternative to polysorbate 80 for delivery of docetaxel. Further, due to the hypoallergenic nature of PSO, the mechanism of pseudoallergy caused by the polyoxyethylene nonionic surfactant was investigated. Based on in vitro cell analysis, it was assumed that the initial contact of polyoxyethylene nonionic surfactant with mast cells provoked pseudoallergy via polyamine receptor-mediated endocytosis.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Chunmeng
authors.initials: C
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Li
authors.affiliation: Chinese Pharmacopoeia Commission, Beijing, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Han
authors.affiliation: National Institute for Food and Drug Control, Beijing, People's Republic of China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Ammar
authors.initials: A
authors.lastname: Ouahab
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yourui
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yerong
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Tu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004058:Diffusion; D000077143:Docetaxel; D006168:Guinea Pigs; D007477:Ions; D053769:Nanocapsules / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D013501:Surface-Active Agents / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007477:Ions; D053769:Nanocapsules; D013501:Surface-Active Agents; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols; C097923:POE sorbitan lanolate
keywords: docetaxel; isosorbide; polyoxyethylene nonionic surfactant; pseudoallergy; sorbitol