Blood–Brain Barrier: Structure and Therapeutic Approaches to Crossing

The blood–brain barrier is a highly selective morphofunctional structure that maintains central nervous system homeostasis and protects it from toxic and foreign substances in the systemic circulation. At the same time, the blood–brain barrier remains a major obstacle to effective pharmacotherapy of central nervous system diseases, as most drugs are unable to cross it. This review discusses current approaches to overcoming the blood–brain barrier, which rely on endogenous transport systems such as adsorptive transcytosis and receptor- or carrier-mediated transcytosis, as well as advanced nano- and biotechnologies. Of particular interest are promising strategies such as modification of therapeutic molecules with cell-penetrating peptides, the use of exosomes and biomimetic nanoplatforms, and cell-mediated delivery of biologically active molecules using autologous leukocytes as “Trojan horses.” Methods for transient disruption of blood–brain barrier integrity (e.g., osmotic modulation and focused ultrasound) and alternative delivery routes, such as intranasal administration providing direct access to the brain via the olfactory and trigeminal nerves, are discussed separately. It is emphasized that successful therapy of central nervous system diseases is not possible without safe, effective, and targeted delivery systems capable of crossing the blood–brain barrier without compromising its protective function. Recent advances in molecular and cellular biology, nanomedicine, and genetic engineering open new horizons for personalized therapeutic approaches aimed at effective traversal of the blood–brain barrier.