Nanoparticle-Based Drug Delivery Across the Blood–Brain Barrier: Current In Vivo Evidence, Translational Challenges, and Future Perspectives

Drug delivery systems based on nanoparticles have emerged as promising approaches for overcoming the blood–brain barrier (BBB), a major obstacle to treating disorders of the central nervous system (CNS). There are several reasons why conventional therapies fail, including poor brain penetration, rapid drug clearance, and nonspecific distribution. This review critically evaluates recent advances in nanoparticle-mediated BBB targeting, focusing particularly on in vivo findings. As part of this review, lipid-based, polymeric, metallic, dendrimeric, exosome-inspired, and magnetic nanoparticles are discussed in conjunction with their transport mechanisms. The review compares their therapeutic efficacy, biodistribution, targeting ability, and safety across a variety of neurological conditions. Additionally, emerging technologies are discussed, including biomimetic nanoparticles, stimuli-responsive systems, artificial intelligence, and personalized nanomedicine. Additionally, this review critically discusses the major barriers to clinical translation, including biosafety, manufacturing, and regulatory challenges. As a result, this review provides an updated perspective on current progress and future prospects for developing effective brain-targeted nanomedicine.