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

Taigen Nakamura, Ryuta Saito, Shin-Ichiro Sugiyama, Yukihiko Sonoda, Toshihiro Kumabe, Teiji Tominaga
Cancer Letters 2011 November 1, 310 (1): 77-83
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.

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