Advancements in Overcoming the Blood-Brain Barrier for Drug Delivery

Abstract

The blood-brain barrier (BBB) presents a significant challenge for the delivery of therapeutic agents to the central nervous system (CNS), effectively protecting the brain from toxins and pathogens while also restricting the entry of potentially beneficial drugs. Recent advances in nanomedicine and drug delivery systems have provided new strategies to bypass or penetrate the BBB, enhancing the treatment of CNS disorders such as brain tumors, Alzheimer's disease, and Parkinson's disease. This review explores the physiology of the BBB, the structural components that contribute to its selective permeability, and the various physiological functions it serves. We discuss the challenges associated with BBB drug delivery and detail several innovative strategies, including receptor-mediated transcytosis, carrier-mediated transport, and nanoparticle-based drug delivery systems. Additionally, the manuscript reviews the in vitro and in vivo models used to evaluate BBB permeability and highlights the latest advancements in enhancing drug delivery to the brain through chemical and physical disruption methods. We provide a comprehensive overview of opportunities for drug delivery across the BBB, focusing on the design of BBB-penetrating molecules and modulation of BBB tight junctions. Finally, this paper examines future directions in BBB research, emphasizing the development of more selective and efficient delivery systems that improve the safety, efficacy, and specificity of CNS-targeted therapies