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

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.

► Effect of local convection-enhanced delivery on blood–brain barrier was examined. ► Local delivery of nimustine hydrochloride transiently opened blood–brain barrier. ► Transient opening was found from about 7–12 days after delivery. ► Systemic chemotherapy during this period prolonged survival of tumor-bearing rats.