Nanoscale drug delivery systems and the blood–brain barrier

Abstract

Renad Alyautdin,1 Igor Khalin,2 Mohd Ismail Nafeeza,1 Muhammad Huzaimi Haron,1 Dmitry Kuznetsov31Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh, Selangor, Malaysia; 2Faculty of Medicine and Defence Health, National Defence University of Malaysia (NDUM), Kuala Lumpur, Malaysia; 3Department of Medicinal Nanobiotechnologies, N. I. Pirogoff Russian State Medical University, Moscow, RussiaAbstract: The protective properties of the blood–brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain's vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual's age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS.Keywords: apoE, blood–brain barrier, CNS, drug targeting, liposomes, nanoparticles