Current approaches to enhance CNS delivery of drugs across the brain barriers

Although many agents have therapeutic potentials for central nervous system (CNS) diseases, few of these agents have been clinically used because of the brain barriers. As the protective barrier of the CNS, the blood-brain barrier and the blood-cerebrospinal fluid barrier maintain the brain microenvironment, neuronal activity, and proper functioning of the CNS. Different strategies for efficient CNS delivery have been studied. This article reviews the current approaches to open or facilitate penetration across these barriers for enhanced drug delivery to the CNS. These approaches are summarized into three broad categories: noninvasive, invasive, and miscellaneous techniques. The progresses made using these approaches are reviewed, and the associated mechanisms and problems are discussed.