Current approaches to facilitate improved drug delivery to the central nervous system.

Although many pharmaceuticals have therapeutic potentials for central nervous system (CNS) diseases, few of these agents have been effectively administered. It is due to the fact that the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSF) restrict them from crossing the brain to exert biological activity. This article reviews the current approaches aiming to improve penetration across these barriers for effective drug delivery to the CNS. These issues are summarized into direct systemic delivery and invasive delivery, including the BBB disruption and convection enhanced delivery. Furthermore, novel drug delivery systems used at the nanoscale, including polymeric nanoparticles, liposomes, nanoemulsions, dendrimers, and micelles are discussed. These nanocarriers could contribute to a breakthrough in the treatment of many different CNS diseases. However, further broadened studies are needed to assess the biocompatibility and safety of these medical devices.

Current Chemical, Biological, and Physiological Views in the Development of Successful Brain-Targeted Pharmaceutics.

One of the greatest challenges with successful pharmaceutical treatments of central nervous system (CNS) diseases is the delivery of drugs into their target sites with appropriate concentrations. For example, the physically tight blood-brain barrier (BBB) effectively blocks compounds from penetrating into the brain, also by the action of metabolizing enzymes and efflux transport mechanisms. However, many endogenous compounds, including both smaller compounds and macromolecules, like amino acids, sugars, vitamins, nucleosides, hormones, steroids, and electrolytes, have their peculiar internalization routes across the BBB. These delivery mechanisms, namely carrier-mediated transport and receptor-mediated transcytosis have been utilized to some extent in brain-targeted drug development. The incomplete knowledge of the BBB and the smaller than a desirable number of chemical tools have hindered the development of successful brain-targeted pharmaceutics. This review discusses the recent advancements achieved in the field from the point of medicinal chemistry view and discusses how brain drug delivery can be improved in the future.