Chemotherapy Delivery Strategies to the Central Nervous System: neither Optional nor Superfluous

Malignant brain tumors including primary brain tumors (e.g., glioblastoma multiforme) and metastases, are aggressive and lethal entities for the majority of affected patients. Current standard treatments involving combinations of surgery, radiotherapy and systemic chemotherapy offer only modest improvements in survival. Faced with dismal survival, great efforts are deployed to find interesting treatment alternatives. However, the blood-brain barrier (BBB) and the blood-tumor barrier (BTB) remain great obstacles to significant drug delivery to brain tumors. The need to optimize delivery strategies for better patient outcome in the treatment of malignant brain tumors is well acknowledged. Certain interesting strategies use surgical or physical techniques to enhance the distribution of therapeutic agents to the central nervous system. The following strategies will be discussed in this review: intra-arterial delivery, osmotic BBB disruption, intranasal delivery, convection-enhanced delivery and osmotic pumps, implanted polymers, magnetic microspheres and ultrasound BBB disruption. The purpose of this paper is to review the importance of the BBB and the BTB and to review the current status and future perspectives of these delivery procedures. Keywords: Blood-brain barrier, blood-brain barrier disruption, brain tumor, chemotherapy, drug delivery, glioblastoma multiforme, targeted delivery.