Breaking through the blood-brain barrier for different kinds of drugs: challenges, solutions, and perspectives

Brain diseases, including psychosis, neurological disorders, strokes, etc., account for more than 15% of all global health damage, which is higher than that caused by cancer and cardiovascular diseases. Brain health and the treatment of brain diseases have become major challenges of the 21st century. The past few decades have witnessed a series of significant advances in human brain science research. The pathogenesis of brain diseases at the molecular and genetic level is being revealed, indicating promising outcomes. However, the existence of the blood-brain barrier (BBB) significantly impedes the delivery of drugs and genes to the brain, which seriously hinders the treatment of brain diseases. This review article provides a brief overview of the concept and history of the BBB. We focus on the critical obstacles and solutions of different kinds of therapeutics, including small molecule drugs, peptides, proteins, and genes, to break through the BBB. Delivery mechanisms, strategies, and vehicles are summarized. Recent advances and efforts in drug delivery studies that aim to overcome the BBB will greatly facilitate the development of brain disease treatment.