Nanoparticle Formulation Derived from Carboxymethyl Cellulose, Polyethylene Glycol, and Cabazitaxel for Chemotherapy Delivery to the Brain

Bioconjug Chem. 2018 Jun 20;29(6):2009-2020. doi: 10.1021/acs.bioconjchem.8b00220. Epub 2018 May 23.

Abstract

Nanoparticles provide a unique opportunity to explore the benefits of selective distribution and release of cancer therapeutics at sites of disease through varying particle sizes and compositions that exploit the enhanced permeability of tumor-associated blood vessels. Though delivery of larger as opposed to smaller and/or actively transported molecules to the brain is prima facie a challenging endeavor, we wondered whether nanoparticles could improve the therapeutic index of existing drugs for use in treating brain tumors via these vascular effects. We therefore selected a family of nanoparticles composed of cabazitaxel-carboxymethyl cellulose amphiphilic polymers to investigate the potential for delivering a brain-penetrant taxane to intracranial brain tumors in mice. Among a small set of nanoparticle formulations, we found evidence for nanoparticle accumulation in the brain, and one such formulation demonstrated activity in an orthotopic model of glioma, suggesting that such nanoparticles could be useful for the treatment of glioma and brain metastases of other tumor types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Brain / drug effects
  • Brain / metabolism
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Carboxymethylcellulose Sodium / chemistry*
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Polyethylene Glycols / chemistry*
  • Taxoids / administration & dosage*
  • Taxoids / chemistry
  • Taxoids / pharmacokinetics
  • Taxoids / therapeutic use

Substances

  • Antineoplastic Agents
  • Taxoids
  • Polyethylene Glycols
  • cabazitaxel
  • Carboxymethylcellulose Sodium