Microneedle-mediated drug delivery systems for brain diseases.

Brain diseases pose a major global health challenge, with the blood-brain barrier (BBB) as the core obstacle for intracranial drug delivery. Microneedles, a minimally invasive technology, can bypass the BBB via intracranial implantation, nose-to-brain, trigeminal nerve, and transdermal systemic routes. This review covers the structural classification, biomaterials, and bypass BBB delivery mechanisms of brain-targeted microneedles. Using glioblastoma, Alzheimer's disease, and Parkinson's disease as models, we overview preclinical microneedle formulations and key signaling pathways, and establish a matching framework linking therapeutic targets, drugs, and microneedle types. We further analyze clinical translation bottlenecks including limited drug loading, unclear long-term biosafety, manufacturing challenges, and regulatory gaps, and propose future directions in technical innovation, standardized evaluation, and regulatory improvement. This work may guide the rational design and clinical translation of microneedle-mediated brain-targeted drug delivery systems.