Cyclodextrin polymers as nanocarriers for sorafenib

Invest New Drugs. 2018 Jun;36(3):370-379. doi: 10.1007/s10637-017-0538-9. Epub 2017 Nov 8.

Abstract

Polymeric nanoparticles based on cyclodextrins are currently undergoing clinical trials as new promising nanotherapeutics. In light of this interest, we investigated cyclodextrin cross-linked polymers with different lengths as carriers for the poorly water-soluble drug sorafenib. Both polymers significantly enhanced sorafenib solubility, with shorter polymers showing the most effective solubilizing effect. Inclusion complexes between sorafenib and the investigated polymers exhibited an antiproliferative effect in tumor cells similar to that of free sorafenib. Polymer/Sorafenib complexes also showed lower in vivo tissue toxicity than with free sorafenib in all organs. Our results suggest that the inclusion of sorafenib in polymers represents a successful strategy for a new formulation of this drug.

Keywords: Anticancer drug; Drug carriers; Nanoparticles; Solubility; Toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Body Weight
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Cellulose / chemistry*
  • Circular Dichroism
  • Cyclodextrins / chemistry*
  • Drug Carriers / chemistry*
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Organ Specificity
  • Solubility
  • Sorafenib / pharmacology*

Substances

  • Cyclodextrins
  • Drug Carriers
  • cyclodextrin polymer
  • Cellulose
  • Sorafenib