Transcellular brain drug delivery: A review on recent advancements

The blood-brain barrier (BBB) has a pivotal role in maintaining brain homeostasis. It robustly protects the brain parenchyma against the invasion of irrelevant substances, which may interrupt its critical function. From a pharmaceutical point of view, such a barrier may cause central nervous system (CNS) disorders refractory by restricting the therapeutics from accessing to their target sites in cerebral parenchyma. On the other side, the increasing rate of CNS disorders demands novel strategies to be developed for effective transferring the drugs through the BBB. Transcellular pathways seem to be more promising in ferrying across the BBB than paracellular route due to using the regular biological routes and retaining the BBB integrity, as well. The transcellular pathway contains several mechanisms for the transportation of therapeutic molecules, which are alternately applicable based on the physicochemical characteristics of the crossing molecule. In the present article, the most considerable transcellular routes, including the adsorptive mediated transcytosis (AMT), receptor-mediated transcytosis (RMT), cell-mediated transcytosis (CMT), and the efflux pumps-mediated drug delivery approaches were reviewed. Exosome, as a new drug carrier, utilizable in various transcellular routes, was also discussed.