Brain-targeting drug delivery systems: The state of the art in treatment of glioblastoma
Bo Sun, Rong Li, Ning Ji, Han Liu, Hongxiang Wang, Chao Chen, Long Bai, Jiacan Su, Juxiang Chen
Abstract
Glioblastoma (GBM) is the most prevalent primary malignant brain tumor, characterized by a high mortality rate and a poor prognosis. The blood-brain barrier (BBB) and the blood-tumor barrier (BTB) present significant obstacles to the efficacy of tumor-targeted pharmacotherapy, thereby impeding the therapeutic potential of numerous candidate drugs. Targeting delivery of adequate doses of drug across the BBB to treat GBM has become a prominent research area in recent years. This emphasis has driven the exploration and evaluation of diverse technologies for GBM pharmacotherapy, with some already undergoing clinical trials. This review provides a thorough overview of recent advancements and challenges in targeted drug delivery for GBM treatment. It specifically emphasizes systemic drug administration strategies to assess their potential and limitations in GBM treatment. Furthermore, this review highlights promising future research directions in the development of intelligent drug delivery systems aimed at overcoming current challenges and enhancing therapeutic efficacy against GBM. These advancements not only support foundational research on targeted drug delivery systems for GBM but also offer methodological approaches for future clinical applications. The prospects for designing drug delivery systems include advancing these systems to clinical applications for the treatment of GBM. • The strategies and applications of non-invasive systemic drug delivery technologies for the treatment of glioblastoma (GBM) are illustrated comprehensively. • The application of cell membrane-coated nanoparticles, which offer a synergistic blend of advantages derived from both nanoparticles and biomimetic materials, is elaborately illustrated. • Extracellular vesicle-based drug delivery for GBM has been studied with a comparative analysis of sources from mammals, bacteria, and plants, highlighting the advantages of each. • Viral vectors, especially adeno-associated viruses, play a significant role in gene therapy for GBM, which is comprehensively discussed. • Highlighting the development objectives and future prospects of targeted drug delivery systems specifically designed for the treatment of GBM. • The challenges encountered by brain-targeted drug delivery systems during their translation to clinical application have been extensively analyzed, and appropriate strategies have been proposed to address them.