Pathophysiological and Etiological Corroborations for the Mechanistic Design of Intranasal Therapies in Glioblastoma Multiforme

The quintessential hallmarks of brain malignancies hinge on their acquired biological traits, which encompass mutations in the epidermal growth factor receptor (EGFR), as well as vasculogenesis and cellular energy reprogramming. Glioblastoma multiforme (GBM) remains a prominent malignant form of brain tumor in humans. GBM patients exhibit a dismal prognosis with a median survival time of only 1-2 years due to the complex pathophysiology, the development of resistance by cancer cells, and the inability of therapeutic components to pass the blood-brain barrier (BBB) and blood-tumor barrier (BTB). BBB, a network of endothelial cells surrounded by astrocyte foot processes, primarily circumvents the transit of therapeutic biomacromolecules and drugs. To address those challenges, targeted therapies to the nose via brain drug delivery have emerged as a steadfast framework for mitigating neurological disorders, bypassing the BBB. A myriad of preclinical paradigms based on intranasal drug approaches utilizing conventional drug therapeutics have been designed and tested for delivering both liquid and solid particle formulations that effectively encapsulate therapeutic biomolecules in brain tissues, especially in GBM. However, there are significant gaps in the effective translation of nose-to-brain delivery approaches for achieving higher drug concentrations of anticancer drugs at the targeted regions in pathological states, such as GBM, without causing damage to healthy tissues. Therefore, the current body of literature aims to corroborate the mechanistic understanding in non-invasive designs using intranasal therapies that efficiently penetrate the BBB and circumvent systemic adverse effects while treating GBM.