Transporter-Mediated Drug Delivery to the Brain

The blood–brain barrier (BBB) formed by the brain capillary endothelial cells with its tight junctions, membrane transporters, and metabolizing enzymes plays an important role in brain protection via restricting the entry of xenobiotics. While efflux transporters expressed at the luminal side of the brain capillary endothelial cells limit the permeation of drugs to the brain by pumping them out to the systemic circulation, the influx transporters mediate the passage of essential nutrients to the brain. The current knowledge about the efflux and influx transporters expressed at the BBB and brain parenchymal cells has been used for the development of several strategies to improve delivery of drugs to the brain. One of the strategies is the modulation of efflux transporter expression, which has been extensively investigated to increase drug delivery of efflux transporter substrates to the brain. In addition, the utilization of influx nutrient transporters expressed in the brain capillary endothelial cells has been used to deliver the drugs via transporter-targeting prodrugs and nanocarriers. The present chapter introduces state-of-the-art knowledge of the recent advances in the utilization of transporters expressed at the BBB to improve drug delivery to the brain. Here, we provide an overview of developed efflux transporter inhibitors as well as transporter-utilizing (pro)drugs and nanocarriers for delivery of drugs to the brain. In addition, we discuss the limitations and advantages of both approaches.