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Pharmaceutical Research

, Volume 29, Issue 9, pp 2398–2406 | Cite as

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

  • Lieselotte De Smet
  • Pieter Colin
  • Wim Ceelen
  • Marc Bracke
  • Jan Van Bocxlaer
  • Jean Paul Remon
  • Chris Vervaet
Research Paper

Abstract

Purpose

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.

Conclusion

Nanosuspensions with a high paclitaxel-to-stabilizer ratio are of interest for the treatment of peritoneal carcinomatosis of ovarian origin via HIPEC.

Key Words

hyperthermic intraperitoneal chemotherapy nanocrystal ovarian cancer paclitaxel wet milling 

Abbreviations

HIPEC

hyperthermic intraperitoneal chemotherapy

MTD

maximum tolerated dose

PEO

polyethylene oxide

Plu F127

Pluronic F127®

Plu F68

Pluronic F68®

PPO

polypropylene oxide

PTX

paclitaxel

TGD

tumor growth delay

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Lieselotte De Smet
    • 1
  • Pieter Colin
    • 2
  • Wim Ceelen
    • 3
  • Marc Bracke
    • 4
  • Jan Van Bocxlaer
    • 2
  • Jean Paul Remon
    • 1
  • Chris Vervaet
    • 1
  1. 1.Laboratory of Pharmaceutical TechnologyGhent UniversityGhentBelgium
  2. 2.Laboratory of Medical Biochemistry and Clinical AnalysisGhent UniversityGhentBelgium
  3. 3.Laboratory of Experimental SurgeryGhent University HospitalGhentBelgium
  4. 4.Department of Experimental OncologyGhent University HospitalGhentBelgium

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