A novel nanoparticle formulation for sustained paclitaxel delivery

W. J. Trickler, A. A. Nagvekar, A. K. Dash

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Purpose: To develop a novel nanoparticle drug delivery system consisting of chitosan and glyceryl monooleate (GMO) for the delivery of a wide variety of therapeutics including paclitaxel. Methods: Chitosan/GMO nanoparticles were prepared by multiple emulsion (o/w/o) solvent evaporation methods. Particle size and surface charge were determined. The morphological characteristics and cellular adhesion were evaluated with surface or transmission electron microscopy methods. The drug loading, encapsulation efficiency, in vitro release and cellular uptake were determined using HPLC methods. The safety and efficacy were evaluated by MTT cytotoxicity assay in human breast cancer cells (MDA-MB-231). Results: These studies provide conceptual proof that chitosan/GMO can form polycationic nano-sized particles (400 to 700 nm). The formulation demonstrates high yields (98 to 100%) and similar entrapment efficiencies. The lyophilized powder can be stored and easily be resuspended in an aqueous matrix. The nanoparticles have a hydrophobic inner-core with a hydrophilic coating that exhibits a significant positive charge and sustained release characteristics. This novel nanoparticle formulation shows evidence of mucoadhesive properties; a fourfold increased cellular uptake and a 1000-fold reduction in the IC 50 of PTX. Conclusion: These advantages allow lower doses of PTX to achieve a therapeutic effect, thus presumably minimizing the adverse side effects.

Original languageEnglish (US)
Pages (from-to)486-493
Number of pages8
JournalAAPS PharmSciTech
Volume9
Issue number2
DOIs
StatePublished - Jun 1 2008

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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