Delivery of taxanes: strategies to develop efficient systems against brain cancers

Gliomas and their metastatic spread to the central nervous system are very challenging diseases. Despite vigorous basic and clinical studies over several decades, the median survival of these patients remains very poor. Standard therapies are surgery plus radiation, implants releasing carmustine, and adjuvant temozolomide, but various new agents are currently under study. This review focuses on a particular class of agents, taxanes, which have significant activity against a variety of tumors, but not against brain cancers. The clinical failure of taxanes may chiefly be attributed to the lack of appropriate drug-delivery systems. Several technologies have been proposed to increase both potency and selectivity, and highly-invasive strategies, such as convectionenhanced diffusion, and intrathecal/intraventricular drug administration, are now available. However, research aims to find lower-risk intravascular drug delivery systems. To gain effective results on CNS cancers, one of the main hindrances is the presence of the blood-brain barrier. This challenges effective intravascular transport and selected drug delivery systems, and demands the adoption of complementary strategies that promote efficient transport through this barrier. Among the various strategies that have been explored, nanovectors (e.g., liposome, micelles, nanoparticles, macromolecular conjugates) may enable the different components to be efficiently assembled. After years of work, some candidates now appear to be emerging that may be relevant in clinical trials. The present review summarizes the most significant approaches, presents emerging research, and highlights directions for further developments in the delivery of taxanes to brain neoplasms.