In this review, we discuss how mutations in glioma are associated with prognosis and treatment efficacy. A fascinating characteristic of glioma and all cancers is that while common growth and developmental pathways are altered, the characteristic mutations are distinct depending on the specific type of tumor with concomitant prognoses. Next-generation sequencing, precision medicine, and artificial intelligence are boosting the employment of molecular biomarkers in cancer diagnosis and treatment. Understanding the biological underpinnings of distinct mutations on critical signaling pathways is crucial for developing novel therapies for glioma.

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.

Rhinosinusitis is a common inflammatory condition of the nasal cavity that often requires antimicrobial and anti-inflammatory therapy. This study aimed to develop a noninvasive, multifunctional nanofiber platform for localized rhinosinusitis treatment. Pullulan-based nanofiber membranes co-loaded with ampicillin and clove oil were fabricated using the scalable Forcespinning® technique. The chemical composition, morphology, and thermo-physical properties of the developed membranes were characterized. Antibacterial activity was evaluated against Staphylococcus aureus using a Kirby - Bauer disk diffusion assay. Cytocompatibility and anti-inflammatory activity were assessed in RAW 264.7 macrophages, while mucus interaction and ex vivo mucosal permeation were evaluated using fluorescence-based methods. The optimized pullulan/ampicillin/clove oil nanofibers exhibited uniform, bead-free morphology with an average diameter of 530 ± 35 nm and adequate thermal stability. Composite nanofibers demonstrated significantly enhanced antibacterial activity compared to single-agent formulations. The nanofibers were non-cytotoxic up to 500 µg/mL and significantly reduced nitric oxide production in LPS-stimulated macrophages (p < 0.05). Mucointeraction and mucosal permeation studies supported their suitability for nasal delivery. These findings demonstrate that pullulan-based nanofibers offer a biocompatible, noninvasive platform for localized antimicrobial and anti-inflammatory therapy in rhinosinusitis.

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 [1]. 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 non‑invasive, 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 [2]. 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.