Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas

Abstract

Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy.

Figure 1. Ommaya reservoir with a catheter placed in the intratumoral cavity following surgical resection, which is an example of local drug delivery

Chemotherapeutic drugs can be placed in the reservoir and the drug will diffuse through the catheter into the surrounding brain parenchyma based on a concentration gradient.

Figure 2. Convection-enhanced delivery with a catheter placed in the intratumoral cavity following surgical resection

Chemotherapeutic drugs can be placed in the reservoir and the drug will move through the catheter into the surrounding brain parenchyma based on a pressure and, to a lesser extent, a concentration gradient.

Figure 3. Drug-impregnated polymers placed in the intratumoral cavity following surgical resection

Chemotherapeutic drugs are impregnated into the biodegradable polymers, which, as a result of degradation, release the drugs in a sustained manner into the surrounding brain parenchyma.