Progress in New Drug Development and Drug Delivery Strategies for Central Nervous System Diseases

The blood-brain barrier (BBB) is a unique feature of the human central nervous system (CNS). Achieving sufficient delivery across the blood-brain barrier (BBB) is important to develop treatments for central nervous system diseases. BBB is a dynamic structure that serves as the most selective physical barrier, allowing less than 2% of small molecule drugs into CNS. Macromolecules are almost blocked by the BBB from reaching the CNS, including recombinant proteins and peptides, antibodies, and viral vectors. Aside from physical barriers, the BBB also exhibits the function as the selective interface for drug transport, such as passive or promoting diffusion and active transport by locating specific transporters in the lumen or abluminal side. Taking together, the BBB presents a significant obstacle to the treatment of central nervous system diseases. Significantly higher concentrations in the circulation or extended administration are demanded to overcome such challenges, which raised the risk of systemic toxicity. Studying strategies to circumvent the BBB is needed to promote drug delivery in central nervous system diseases.

Adsorptive-mediated transcytosis (AMT), carrier-mediated transcytosis (CMT), and receptor-mediated transcytosis (RMT) are the current main approaches for drug delivery to bypass BBB. However, a ‘turn-key’ platform for drug delivery across BBB is not yet established. Defining target receptors or carrier proteins which is highly expressed in the endothelial cells of the cerebral vasculature, especially those in the microvascular capillary beds, is the key point for designing novel strategies for CMT and RMT. Aging-related central nervous system diseases, including AD and PD, can alter the expression levels of target receptors or carrier proteins, as well as alter basement membrane physicochemical properties and enzyme distribution. In-depth learning of the full landscape of BBB provides powerful tools for new drug design or delivery strategies in aging-related central nervous system diseases.

This Research Topic aims to provide a forum for investigators to review and expand knowledge about the relevancy of aging-related central nervous system diseases and BBB, ultimately identifying specific new ideas for designing drugs for aging-related central nervous system diseases.

We welcome submissions in the form of Review and Original Research manuscripts that discuss the following topics:
- BBB Landscape in aging-related central nervous system diseases
-Novel Strategies for delivering drugs across BBB
-New drugs on aging-related central nervous system diseases