title: Hypersensitivity reaction studies of a polyethoxylated castor oil-free,             liposome-based alternative paclitaxel formulation.
abstract: The commercial drug paclitaxel (Taxol) may introduce hypersensitivity reactions             associated with the polyethoxylated castor oil-ethanol solvent. To overcome these             problems, we developed a polyethoxylated castor oil-free, liposome-based alternative             paclitaxel formulation, known as Lipusu. In this study, we performed in vitro             and in vivo experiments to compare the safety profiles of Lipusu and Taxol, with             special regard to hypersensitivity reactions. First, Swiss mice were used to determine             the lethal dosages, and then to evaluate hypersensitivity reactions, followed             by histopathological examination and enzyme-linked immunosorbent assays (ELISAs)             of serum SC5b-9 and lung histamine. Additionally, healthy human serum was used             to analyze in vitro complement activation. Finally, an MTT assay was used to determine             the in vitro anti-proliferation activity. Our data clearly showed that Lipusu             displayed a much higher safety margin and did not induce hypersensitivity or hypersensitivity-related             lung lesions, which may be associated with the fact that Lipusu did not activate             complement or increase histamine release in vivo. Moreover, Lipusu did not promote             complement activation in healthy human serum in vitro, and demonstrated anti-proliferative             activity against human cancer cells, similar to that of Taxol. Therefore, the             improved formulation of paclitaxel, which exhibited a much better safety profile             and comparable cytotoxic activity to Taxol, may bring a number of benefits to             cancer patients.
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai 264005, PR China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Cheng
authors.forename: Yuan
authors.initials: Y
authors.lastname: Du
authors.forename: Liang
authors.initials: L
authors.lastname: Ye
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Chen
authors.forename: Leiming
authors.initials: L
authors.lastname: Zhang
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.forename: Jingwei
authors.initials: J
authors.lastname: Tian
authors.forename: Fenghua
authors.initials: F
authors.lastname: Fu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D002368:Castor Oil / Q000031:analogs & derivatives* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000032:analysis; D003165:Complement System Proteins / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006632:Histamine / Q000032:analysis; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism / Q000473:pathology; D008081:Liposomes / Q000737:chemistry*; D008168:Lung / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015938:Complement Membrane Attack Complex; D008081:Liposomes; C047610:SC5b-9 protein complex; C023040:polyethoxylated castor oil; D002368:Castor Oil; D006632:Histamine; D003165:Complement System Proteins; D017239:Paclitaxel