Surgically Mediated Drug Delivery Techniques

Despite recent insights into the pathobiology underlying central nervous system (CNS) malignant gliomas (MGs) and the development of new putative therapeutic compounds to treat these neoplasms, there remains no curative surgical or medical treatment for these tumors. Extensive surgical resection has been shown to prolong survival but is not a total cure because of widespread infiltrative microscopic disease that extends well beyond the macroscopic or imaging-defined tumor boundaries and outside of what can be feasibly removed.17,36 The effectiveness of radiation therapy is limited by the intolerance of normal brain parenchyma and results in variable failure patterns. Because of the limitations associated with surgery and radiotherapy, investigation into adjuvant chemobiological agents to treat these tumors has been undertaken. Although a rapidly expanding number of promising therapeutic agents have been developed, antineoplastic regimens have remained unsuccessful in treating MG primarily because of ineffective drug delivery to neoplastic cells. Currently available delivery paradigms for distribution of antineoplastic agents to the CNS include nonsurgical and surgically mediated techniques. Nonsurgical methods of CNS drug delivery include systemic and intrathecal or intraventricular administration. Systemic delivery is restricted by systemic toxicity, nontargeted distribution, and the inability of most substances to traverse the blood–brain barrier. Diffusion-dependent methods, including intrathecal or intraventricular administration, are limited by nontargeted delivery, inhomogeneous dispersion, and ineffective distribution. To overcome these limitations, investigation of surgically mediated drug delivery methods, including implantation of drugimpregnated polymers and direct convection-enhanced delivery (CED) of therapeutic compounds, has been performed.1,18