Nose-to-brain delivery: exploring newer domains for glioblastoma multiforme management

Glioblastoma multiforme (GBM) is the most common and aggressive form of the primary brain tumors in humans. The intricate pathophysiology, the development of resistance by tumor cells, and the inability of the drugs to effectively cross the blood-brain and blood-tumor barriers result in poor prognosis for GBM patients, with a median survival time of only 1 to 2 years. Nose-to-brain delivery offers an attractive, noninvasive strategy to enhance drug penetration or transport novel drug/gene carriers into the brain. Although the exact mechanism of intranasal delivery remains elusive, the olfactory and trigeminal nerve pathways have been found to play a vital role in circumventing the traditional barriers of brain targeting. This review discusses the intranasal pathway as a novel domain for delivering drugs and nanocarriers encapsulating drugs/genes, as well as stem cell carriers specifically to the glioma cells. Considering the fact that most of these studies are still in preclinical stage, translating such intranasal delivery strategies from bench to bedside would be a critical step for better management and prognosis of GBM. Graphical abstract.