Nanotechnology-Driven Strategies for Enhanced Brain Drug Delivery: A Review of Bio-Nanoparticle Systems

The BBB is one of the biggest challenges in the treatment of neurological diseases, as it blocks more than 98% of drugs reaching the brain. In this review, current nanotech approaches to overcoming the BBB are compiled, including functionalized NPs (liposomes, polymeric NPs, SLNs, and inorganic NPs) with different modifications for targeting, including RMT, CPPs, positive charges, and non-invasive methods of administration such as intranasal delivery and MRgFUS. In parallel, biomimetic systems based on exosomes and cell membrane-coated NPs were reported. Examples are provided for the treatment of AD, PD, and GBM. Despite the impressive results at the preclinical stage, major challenges, including chronic toxicity, immunogenicity, manufacturing capacity, and regulatory issues, should be addressed before translation to clinical settings. The future of the brain-targeted delivery of drugs lies in the integration of personalized medicine, hybrid nanocarriers and real-time imaging.