Local convection-enhanced delivery of chemotherapeutic agent transiently opens blood-brain barrier and improves efficacy of systemic chemotherapy in intracranial xenograft tumor model

Cancer Lett. 2011 Nov 1;310(1):77-83. doi: 10.1016/j.canlet.2011.06.018. Epub 2011 Jun 28.

Abstract

Recently, local chemotherapy proved its efficacy against malignant gliomas. Under the hypothesis that local delivery of chemotherapeutic agents into the brain parenchyma induce opening of the blood-brain barrier (BBB), we evaluated the opening of BBB after convection-enhanced delivery of nimustine hydrochloride into the brain parenchyma. Local convection-enhanced delivery of nimustine hydrochloride transiently opened the BBB from about 7-12 days after delivery in normal rodent brain. Systemic chemotherapy during this period of BBB disruption had synergistic effects resulting in prolonged survival of tumor-bearing rats. The present strategy may provide a new approach for glioma chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Blood-Brain Barrier / drug effects*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Convection
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Drug Delivery Systems / methods*
  • Gliosarcoma / drug therapy*
  • Gliosarcoma / pathology
  • Kaplan-Meier Estimate
  • Male
  • Nimustine / administration & dosage*
  • Nimustine / adverse effects
  • Rats
  • Rats, Inbred F344
  • Rats, Sprague-Dawley
  • Treatment Outcome
  • Xenograft Model Antitumor Assays*

Substances

  • Antineoplastic Agents
  • Nimustine
  • Doxorubicin