title: Paclitaxel nanosuspensions for targeted chemotherapy - nanosuspension preparation, characterization, and use.
abstract: OBJECTIVE
  The purpose of this work was to prepare a stable paclitaxel nanosuspension and test it for potential use as a targeted chemotherapeutic. Different particle coatings were employed to assess their impact on cellular uptake in vitro. In vivo work was then performed to demonstrate efficacy in tumor-bearing mouse models.
  
  
  METHODS
  Paclitaxel nanosuspensions were prepared using a homogenization process and coated with excipients. Surface charge was measured by zeta potential, potency by high-performance liquid chromatography, and solubility using an in-line UV probe. Cellular uptake studies were performed via flow cytometry. In vivo experiments were performed to determine residence time, maximum tolerated dose, and the efficacy of paclitaxel nanosuspensions (Paclitaxel-NS).
  
  
  RESULTS
  A stable paclitaxel nanosuspension was prepared and coated with various excipients. Studies in mice showed that the nanosuspension was well-tolerated and at least as effective as the IV Taxol control in prolonging mouse survival in a head and neck cancer model as well as an ovarian cancer model with a lower overall drug dose than the traditional IV administration route.
  
  
  CONCLUSIONS
  The paclitaxel nanosuspension is suitable for cellular uptake. The nanosuspension was effective in prolonging life in two separate xenograft orthotopic murine cancer models through two separate routes of administration.
authors.affiliation: Baxter Healthcare Corporation , Round Lake, IL , USA and.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lee
authors.forename: Shawn F
authors.initials: SF
authors.lastname: Bairstow
authors.forename: Jane O
authors.initials: JO
authors.lastname: Werling
authors.forename: Mahesh V
authors.initials: MV
authors.lastname: Chaubal
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lin
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Murphy
authors.forename: James P
authors.initials: JP
authors.lastname: DiOrio
authors.forename: Jerome
authors.initials: J
authors.lastname: Gass
authors.forename: Barrett
authors.initials: B
authors.lastname: Rabinow
authors.forename: Xiaoen
authors.initials: X
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yang
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005079:Excipients / Q000737:chemistry; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000737:chemistry* / Q000494:pharmacology; D013535:Suspensions / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D005079:Excipients; D013535:Suspensions; D017239:Paclitaxel