Breaking Barriers: Advancements in CNS Drug Delivery for Glioblastoma.

Glioblastoma is known as the most aggressive primary brain tumor in adults, and it is still largely not curable, with a median survival of approximately 15 months when standard multimodal therapy is applied. The standard treatment nowadays is maximal safe surgical resection, associated with radiotherapy and temozolomide. Treatment effectiveness is limited not only by an impassable blood-brain barrier (BBB) to drug delivery to the brain, but also by the heterogeneity of the tumors and intrinsic or acquired drug resistance, resulting in a certain and inescapable tumor relapse. Therefore, novel drug delivery systems are being designed to overcome the BBB and improve therapeutic efficacy. These approaches include nanoparticle-mediated delivery systems, convection-enhanced intra-tumoral infusion, implantable drug-releasing devices, and noninvasive focused ultrasound technology, which induced transient disruption of the BBB. These approaches are designed to enhance local drug exposure and reduce systemic toxicity with promising preclinical and early clinical results. However, many clinical and technical challenges remain, especially the need for safety, homogeneous drug delivery, and translation of these advances into effective clinical therapies. Current glioblastoma treatment landscape and opportunities include maturing delivery systems, novel therapeutic approaches, including targeted molecular therapies and immunotherapy, as well as personalized regimens. This multidisciplinary modality may have the capacity to help not only patients with GBM but others as well through a multimodal approach of targeted drug delivery and innovative therapy in the long run to improve clinical outcomes of GBM in patients.