title: Paclitaxel nanosuspensions coated with P-gp inhibitory surfactants: I. Acute toxicity and pharmacokinetics studies.
abstract: OBJECTIVE
  The aim of the present study was to evaluate the acute toxicity and pharmacokinetics of paclitaxel nanosuspensions stabilized with TPGS in mice.
  
  
  METHODS
  The paclitaxel nanosuspensions were prepared by evaporative precipitation into aqueous solution (EPAS) method, and freeze-dried powders of the nanosuspensions were obtained through lyophilization process. The morphology and particle size of nanosuspensions were determined by transmission electron microscope and Zetasizer, respectively. The acute toxicity and pharmacokinetics of paclitaxel nanosuspensions after intravenous administration to Kunming mice were studied. A marketed paclitaxel injectable solution was studied parallelly.
  
  
  RESULTS
  The paclitaxel nanoparticles were in rod shape under transmission electron microscope, and their mean particle size was 135.4 ± 5.7 nm. Results of acute toxicity showed the LD50 of paclitaxel nanosuspensions was 98.63 mg/kg, twice more than that of the marketed injection (41.46 mg/kg). After intravenous injection paclitaxel nanosuspensions displayed different pharmacokinetic properties in comparison with the marketed injectable solution, including a decreased initial drug concentration, increased plasma half-life, AUC and MRT.
  
  
  CONCLUSIONS
  The paclitaxel nanosuspensions prepared in this study could markedly enhance the tolerance dosage in mice, and manifest different pharmacokinetic properties compared with the solution.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China. Electronic address: business_gaolei@yahoo.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China. Electronic address: liuguiy@gmail.com.
authors.forename: Guiyang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Niu
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity* / Q000648:ultrastructure; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*; D013535:Suspensions; D023382:Toxicity Tests, Acute; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D020099:Coated Materials, Biocompatible; D013501:Surface-Active Agents; D013535:Suspensions; D014810:Vitamin E; D011092:Polyethylene Glycols; C014225:tocophersolan; D017239:Paclitaxel
keywords: Acute toxicity; Colloidal drug delivery system; Nanosuspensions; Paclitaxel; Pharmacokinetics