Paclitaxel-clusters coated with hyaluronan as selective tumor-targeted nanovectors

Ilia Rivkin, Keren Cohen, Jacob Koffler, Dina Melikhov, Dan Peer, Rimona Margalit

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

Paclitaxel (PTX) is a widely used anti-tumor agent in the treatment of solid tumors. Lack of selective strategies to target PTX into tumor cells together with poor solubility necessitating detergent, are severe clinical limitations. To address these hurdles, we devised a strategy that utilized PTX insolubility, mixing it with lipids that self-assemble into nanoparticle-like clusters. These clusters were then coated with hyaluronan, a glycosaminoglycan (GAG), and termed PTX-GAGs. These particles, delivered PTX selectively into tumor cells in a CD44-dependent manner. Injected systemically to mice bearing solid tumors, the PTX-GAGs showed high safety profile and tumor accumulation. Tumor progression was exponential upon treatment with free PTX or PTX in albumin nanoparticles (the FDA-approved Taxol® and Abraxane®, respectively). Under the same conditions, PTX-GAGs induced tumor arrest and were as potent as a 4-fold higher Taxol® dose. Our findings suggest GAGs merit further investigation as vehicles for taxanes, and may be applicable as carriers in other therapeutic settings.

Original languageEnglish (US)
Pages (from-to)7106-7114
Number of pages9
JournalBiomaterials
Volume31
Issue number27
DOIs
StatePublished - Sep 2010

Keywords

  • Abraxane
  • Drug delivery
  • Hyaluronan
  • Paclitaxel
  • Tumor targeting

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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