Nasal Drug Delivery of Anticancer Drugs for the Treatment of Glioblastoma: Preclinical and Clinical Trials

Abstract

Glioblastoma (GBM) is the most lethal form of brain tumor, being characterized by the rapid growth and invasion of the surrounding tissue. The current standard treatment for glioblastoma is surgery, followed by radiotherapy and concurrent chemotherapy, typically with temozolomide. Although extensive research has been carried out over the past years to develop a more effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in terms of the overall survival of patients. Consequently, new therapeutic approaches are urgently needed. Overcoming the blood–brain barrier (BBB) is a major challenge in the development of therapies for central nervous system (CNS) disorders. In this context, the intranasal route of drug administration has been proposed as a non-invasive alternative route for directly targeting the CNS. This route of drug administration bypasses the BBB and reduces the systemic side effects. Recently, several formulations have been developed for further enhancing nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review is to provide an overview of the strategies that have been developed for delivering anticancer compounds for the treatment of GBM while using nasal administration. In particular, the specific properties of nanomedicines proposed for nose-to-brain delivery will be critically evaluated. The preclinical and clinical data considered supporting the idea that nasal delivery of anticancer drugs may represent a breakthrough advancement in the fight against GBM.

Fenbendazole Controls In Vitro Growth, Virulence Potential, and Animal Infection in the Cryptococcus Model

“…For instance, midazolam, a benzodiazepine depressant, reaches clinically effective concentrations within less than 10 min after nasal administration in humans (41). The low molecular mass of fenbendazole (299.349 g/mol) also favors brain absorption after intranasal administration (42). These findings agree with our current results showing that all animals infected with C. neoformans and treated with fenbendazole intranasally survived.…”

Engineering precision nanoparticles for drug delivery

“…Thus, intranasal administration has been increasingly explored as an option for NP delivery to the brain as it bypasses the BBB and avoids many of the limitations of systemic delivery 115,131 . However, factors such as a limited dosing volume and variables attributed to patient congestion and mucus have presented notable obstacles to the intranasal route 132,133 .…”

Focused Ultrasound and Microbubbles-Mediated Drug Delivery to Brain Tumor

“…Various therapeutic agents, such as small organic molecules, biotech complexes, and stem cells, are under investigation for GBM treatment via nose-to-brain delivery. Also, several nanostructured and nano-sized carrier systems were designed for enhancing intranasal delivery [ 30 ]. However, the majority of studies at present are in the pre-clinical phase of development, where favorable results remain under animal models.…”