Clinical translation of nanomedicines for brain diseases: Current challenges and future directions

Since the approval of Doxorubicin Liposomal (Doxil®) by the U.S. Food and Drug Administration (FDA) in 1995, the field of nanomedicine has undergone substantial growth, transforming the landscape of drug delivery. Nanomedicine offers innovative approaches to enhance the pharmacokinetics and pharmacodynamics of conventional therapeutic agents. Notably, nanomedicine facilitates targeted and multifunctional drug delivery as well as enabling at-site controlled drug release, improving therapeutic precision and minimizing off-target effects. To date, over 50 nanomedicines have received regulatory approval for the treatment of various diseases, with more than 100 currently undergoing clinical trials. However, despite these great advancements, the application of nanomedicines in treating brain diseases remains limited. The blood-brain barrier (BBB) hurdle and the intricate complexity of the central nervous system (CNS) significantly hinder the development of brain-targeted nanotherapeutics. In this review, we will summarize the current challenges encountered in developing nanomedicines for brain diseases and explore potential strategies to overcome these barriers, aiming to accelerate their translation into clinical practice.