Frontiers in Drug Discovery · Published 2026-06-10 · DOI 10.3389/fddsv.2026.1861506
Sara Palladino, Lorenzo Emiliano Imbò, Daniela Benigno, Oluwasegun Eric Ajayi, Simone Braccia, Francesca Fasano, Annarita Falanga, Rosa Bellavita, Stefania Galdiero
Glioblastoma multiforme (GBM) is the most aggressive brain tumor and remains one of the most difficult malignancies to treat. The main obstacle in GBM treatment is the limited ability of most drugs to cross the blood-brain barrier (BBB), which together with the heterogeneity and complexity of GBM, contributes to therapeutic failure, drug resistance, and poor clinical translation. Moreover, despite only a few agents (temozolomide, lomustine, carmustine, and bevacizumab) have received approval from the U.S. Food and Drug Administration (FDA), their efficacy remains modest and there is the need to design more effective strategies. In this context, to address these limitations associated with conventional drug administration, biomaterials-based delivery systems have emerged as promising platform for their biodegradability, ability to enhance BBB penetration, promote drug accumulation at the tumor site, and ultimately improve therapeutic efficacy. In this review, we provide a critical description of the natural and synthetic biomaterials outlining their physicochemical properties, advantages for the fabrication of delivery systems and their limitations in preclinical and clinical settings. Further, we also provide a comprehensive overview of biomaterials functionalized with therapeutic agents for GBM treatment, highlighting their composition, delivery strategies, and preclinical and clinical outcomes. Overall, by bridging biomaterial design with tumor biology, this review aims to identify novel directions for the development of innovative biomaterials-based drug delivery systems to improve therapeutic options in GBM treatments.
Abstract from DOAJ. Public domain (CC0 1.0).
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Palladino, S., Imbò, L., Benigno, D., et al. (2026). Engineering hope: biomaterial strategies against glioblastoma. Frontiers in Drug Discovery. https://doi.org/10.3389/fddsv.2026.1861506