title: Development of a nanocrystalline Paclitaxel formulation for HIPEC treatment.
abstract: OBJECTIVE
  To develop a nanocrystalline paclitaxel formulation with a high paclitaxel-to-stabilizer ratio which can be used for hyperthermic intraperitoneal chemotherapy (HIPEC).
  
  
  METHODS
  Paclitaxel (PTX) nanocrystals were prepared via wet milling using Pluronic F127(®) as stabilizer. The suitability of paclitaxel nanosuspensions for HIPEC treatment was evaluated by analyzing the cytotoxicity of both stabilizer and formulation, and by determining the maximum tolerated dose (MTD) and bioavailability. The effect on tumor growth was evaluated by magnetic resonance imaging (MRI) at day 7 and 14 after HIPEC treatment in rats with peritoneal carcinomatosis of ovarian origin.
  
  
  RESULTS
  Monodisperse nanosuspensions (±400 nm) were developed using Pluronic F127(®) as single additive. The cytotoxicity and MTD of this nanocrystalline formulation was similar compared to Taxol(®), while its bioavailability was higher. MRI data after HIPEC treatment with a PTX nanocrystalline suspension showed a significant reduction of tumor volume compared to the non-treated group. Although no significant differences on tumor volume were observed between Taxol(®) and the nanosuspension, the rats treated with the nanosuspension recovered faster following the HIPEC procedure.
  
  
  CONCLUSIONS
  Nanosuspensions with a high paclitaxel-to-stabilizer ratio are of interest for the treatment of peritoneal carcinomatosis of ovarian origin via HIPEC.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
authors.forename: Lieselotte
authors.initials: L
authors.lastname: De Smet
authors.forename: Pieter
authors.initials: P
authors.lastname: Colin
authors.forename: Wim
authors.initials: W
authors.lastname: Ceelen
authors.forename: Marc
authors.initials: M
authors.lastname: Bracke
authors.forename: Jan
authors.initials: J
authors.lastname: Van Bocxlaer
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D003460:Crystallization; D005260:Female; D008854:Microscopy, Electron; D036103:Nanotechnology; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010534:Peritoneal Neoplasms / Q000188:drug therapy; D051381:Rats
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel