Nanoparticles for Brain Tumor Delivery

Brain cancers and metastases are often highly fatal and represent a complex therapeutic challenge. The unique location of brain tumors within the cranial cavity and behind the blood-brain barrier (BBB) shields tumor cells from systemically administered therapeutics. Nanoparticulate carriers can deliver high, sustained doses of therapeutic agents to tumors because of their size and particulate nature, and can be retained within the tumor interstitium for extended drug exposure. However, nanoparticles also encounter unique obstacles to delivery compared with small molecular-weight agents. The unique structure and composition of the BBB restricts tumor entry of particulates, and the dense interstitium hinders nanoparticle transport within the tumor. However, components of the BBB and extracellular matrix may be targeted to open microvasculature transiently, enhance tumor perfusion and permeability, and increase nanoparticle penetration. Furthermore, antibody derivatization of nanoparticles to target receptors associated with endocytic transport machinery in endothelial cells can induce transcellular passage of drugs into the interstitium. In this chapter, we review current strategies in nanoparticle design and delivery to overcome the unique physiological barriers to drug delivery in patients with brain tumors.