Bridging the Lab-to-Clinic Gap in Intranasal Nanomaterial-Based Chemotherapy for Glioblastoma

Clinical outcomes for brain cancer are often poor because the blood–brain/tumor barrier hinders effective drug delivery to malignant tissue. Glioblastoma, the most common primary brain malignancy in adults, has an average survival of approximately fourteen months. Here, we discuss novel strategies that our research group and others are developing to deliver chemotherapy to the brain via the nasal cavity. Although significant hurdles remain, intranasal delivery holds substantial promise for improving outcomes for patients with brain cancer. Intranasal delivery is noninvasive, permits repeated dosing, and has been shown to enable direct nose-to-brain transport that bypasses the blood–brain barrier. Challenges such as accurately targeting drugs to the appropriate region of the nasal cavity at therapeutically relevant doses, while maintaining reproducibility, make this cutting-edge approach a regulatory challenge. The prolonged path to clinical translation discourages many researchers from pursuing this potentially life-saving strategy. Nevertheless, preclinical studies demonstrate that intranasal delivery can achieve up to ten-fold higher concentrations of select drugs in the brain. Cancer chemotherapeutics span a wide range of molecular formats, from small molecules to 150-kilodalton antibodies. Accordingly, delivery strategies must be carefully matched to the molecular properties of each therapeutic. Here, we focus on the intranasal delivery of small molecule inhibitors using nanomaterial-based platforms, including aerosols, lipids, gold nanoparticles, gels, emulsions, fibers, and their combinations. Ultimately, we hope that intranasal delivery approaches will be translated to provide patients with better therapeutic outcomes.