Novel delivery strategies for glioblastoma

Abstract

Brain tumors--particularly glioblastoma multiforme--pose an important public health problem in the United States. Despite surgical and medical advances, the prognosis for patients with malignant gliomas remains grim: current therapy is insufficient with nearly universal recurrence. A major reason for this failure is the difficulty of delivering therapeutic agents to the brain: better delivery approaches are needed to improve treatment. In this article, we summarize recent progress in drug delivery to the brain, with an emphasis on convection-enhanced delivery of nanocarriers. We examine the potential of new delivery methods to permit novel drug- and gene-based therapies that target brain cancer stem cells and discuss the use of nanomaterials for imaging of tumors and drug delivery.

Figure 1

Representative drug distributions for a) diffusion-based implant systems, such as Gliadel®, b) CED of drug solutions, and c) CED of drug-loaded nanomaterials

Figure 2

Nanomaterials used in drug delivery. A: Polymeric nanoparticles (NPs) are typically made of biodegradable polymers. B: Liposomes are composed of phospholipids. C: Polymeric micelles are formed in an aqueous environment from the association of block copolymers. D: Dendrimers are branched, tree-like polymers, allowing drugs to be attached to its many arms. E: Carbon nanotubes, made of benzene rings, can carry drugs inside the lumen of the tube or attached to the sides. Reproduced from Bennewitz and Saltzman (141), with permission

Figure 3

T1-MRI of Gd-DTPA (green) and ¹²⁴I-labelled (red) human serum albumin coinfusion at 24 hours (A and C) and 72 hours (B and D). Note the large but imperfect area of overlap (yellow). Reproduced from (123), permission pending.