Drug Repurposing and Overcoming the Blood-Brain Barrier for Glioblastoma

Glioblastoma (GBM) is the most aggressive form of primary brain tumor in adults, marked by rapid growth, widespread infiltration, and resistance to standard therapies. A key challenge in treating GBM is the blood-brain barrier (BBB), which restricts the delivery of therapeutic agents to the central nervous system (CNS). Drug repurposing—finding new therapeutic uses for existing drugs—offers a promising, cost-effective strategy to overcome this hurdle. This chapter explores the structural and functional complexities of the BBB, emphasizing its transport mechanisms and recent advances in drug delivery strategies, such as nanocarriers, focused ultrasound, and receptor-mediated transcytosis, to improve CNS penetration. It also reviews repurposed drugs capable of crossing the BBB and showing efficacy against GBM, including antipsychotics, antimalarials, anti-inflammatory agents, and metabolic…