Drug delivery to brain tumors - PubMed (original) (raw)

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Drug delivery to brain tumors

Jaishri Blakeley. Curr Neurol Neurosci Rep. 2008 May.

Abstract

A prerequisite for the efficacy of any cancer drug is that it reaches the tumor in therapeutic concentrations. This is difficult to accomplish in most systemic solid tumors because of factors such as variable hypoxia, intratumoral pressure gradients, and abnormal vasculature within the tumors. In brain cancer, the situation is complicated by the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier, which serve as physical and physiologic obstacles for delivery of drugs to the central nervous system. Many approaches to overcome, circumvent, disrupt, or manipulate the BBB to enhance delivery of drugs to brain tumors have been devised and are in active investigation. These approaches include high-dose intravenous chemotherapy, intra-arterial drug delivery, local drug delivery via implanted polymers or catheters, BBB disruption, and biochemical modulation of drugs.

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Figure 1

Figure 1

Schematic of the components of the blood-brain barrier (BBB), includ ing endothelial cells with tight junctions, pericytes, basement membrane, drug efflux transporters, and astrocytic foot processes. Various mechanisms for transport across the BBB, including transcellular diffusion, absorptive endocytosis, carrier-mediated transport, and receptor-mediated transcytosis, are also represented. Finally, approaches to deliver drugs directly to the brain and to assess drug concentration within brain tissue are displayed. ATP—adenosine triphosphate; BCRP—breast cancer resistance protein; CED—convection-enhanced delivery; MRP—multidrug resistance protein; P-gp—P glycoprotein.

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