title: Evaluation of the efficacy, toxicity and safety of vinorelbine incorporated in a lipid emulsion.
abstract: To reduce the severe adverse effects of vinorelbine (VRB) with the aim of improving patient compliance, a parenteral vinorelbine-loaded lipid emulsion (VLE) has been developed. The objective of the present study was to get insight into the preclinical antitumor efficacy, toxicity and safety of VLE, and compare this with that of the commercial product, Navelbine(®) i.v. (VS). Comparable antitumor efficacy of VLE and VS was observed in tumor-bearing nude mouse models inoculated with A549 human lung cancer, hepatoma solidity (Heps) G2 cancer and BCAP-37 human breast cancer cells. The median lethal dose (LD(50)) in mice was 29.3mg/kg (male) and 32.1mg/kg (female) for VLE, while the corresponding value was 30.5mg/kg (male and female) for VS. In the long-term toxicity study, VLE significantly reduced the decreases in RBC, HC, WBC and WBC differential count (DC) levels. Lesions in spleen, thymus, lymph nodes, bone marrow, testis, ovary and injection site induced by VS were much more severe compared with VLE. VLE also exhibited less local venous irritation than VS, as well as no hemolysis or hypersensitivity. Consequently, these observations clearly indicate that the lipid emulsion could be a useful potential parenteral carrier for VRB with equivalent efficacy and lower toxicity.
authors.affiliation: Department of Pharmaceutics, Shen yang Pharmaceutical University, Wenhua Road 103, Shen yang 110016, Liaoning Province, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhao
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Luo
authors.forename: Xia
authors.initials: X
authors.lastname: Lin
authors.forename: Lishuang
authors.initials: L
authors.lastname: Xu
authors.forename: Haibing
authors.initials: H
authors.lastname: He
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D004655:Emulsions; D005260:Female; D006801:Humans; D006967:Hypersensitivity; D007263:Infusions, Parenteral; D007509:Irritants / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D007928:Lethal Dose 50; D008055:Lipids / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D008819:Mice, Nude; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004655:Emulsions; D007509:Irritants; D008055:Lipids; D014747:Vinblastine; D000077235:Vinorelbine