title: Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings.
abstract: BACKGROUND
  Considering the observations that linoleic acid conjugated with paclitaxel (CLA-PTX) possesses antitumor activity against brain tumors, is able to cross the blood-brain barrier, but has poor water solubility, the purpose of this study was to prepare a novel CLA-PTX microemulsion and evaluate its activity against brain tumors in vitro and in vivo.
  
  
  METHODS
  The in vitro cytotoxicity of a CLA-PTX microemulsion was investigated in C6 glioma cells. The in vivo antitumor activity of the CLA-PTX microemulsion was evaluated in tumor-bearing nude mice and rats. The pharmacokinetics of the CLA-PTX microemulsion were investigated in rats, and its safety was also evaluated in mice.
  
  
  RESULTS
  The average droplet size of the CLA-PTX microemulsion was approximately 176.3 ± 0.8 nm and the polydispersity index was 0.294 ± 0.024. In vitro cytotoxicity results showed that the IC(50) of the CLA-PTX microemulsion was 1.61 ± 0.83 μM for a C6 glioma cell line, which was similar to that of free paclitaxel and CLA-PTX solution (P > 0.05). The antitumor activity of the CLA-PTX microemulsion against brain tumors was confirmed in our in vivo C6 glioma tumor-bearing nude mice as well as in a rat model. In contrast, Taxol(®) had almost no significant antitumor effect in C6 glioma tumor-bearing rats, but could markedly inhibit growth of C6 tumors in C6 glioma tumor-bearing nude mice. The pharmacokinetic results indicated that CLA-PTX in solution has a much longer circulation time and produces higher drug plasma concentrations compared with the CLA-PTX microemulsion. The results of the acute toxicity study showed that the LD(50) of CLA-PTX solution was 103.9 mg/kg. In contrast, the CLA-PTX microemulsion was well tolerated in mice when administered at doses up to 200 mg/kg.
  
  
  CONCLUSIONS
  CLA-PTX microemulsion is a novel formulation with significant antitumor efficacy in the treatment of brain tumors, and is safer than CLA-PTX solution.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.forename: Jie-Si
authors.initials: JS
authors.lastname: Li
authors.forename: Xi-Yu
authors.initials: XY
authors.lastname: Ke
authors.forename: Yu
authors.initials: Y
authors.lastname: Duan
authors.forename: Ruo
authors.initials: R
authors.lastname: Du
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.forename: Ke-Fu
authors.initials: KF
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Xing-Huo
authors.initials: XH
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D007928:Lethal Dose 50; D019787:Linoleic Acid / Q000737:chemistry*; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry* / Q000633:toxicity; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004655:Emulsions; D053769:Nanocapsules; D019787:Linoleic Acid; D017239:Paclitaxel