Smart Strategies for Therapeutic Agent Delivery into Brain across the Blood-Brain Barrier Using Receptor-Mediated Transcytosis.

Smart Strategies for Therapeutic Agent Delivery into Brain across the Blood-Brain Barrier Using Receptor-Mediated Transcytosis. Chem Pharm Bull (Tokyo). 2020;68(4):316-325 Authors: Tashima T Abstract Discriminatory drug delivery into target cells is essential to effectively elicit the drug activity and to avoid off-target side effects; however, transporting drugs across the cell membrane is difficult due to factors such as molecular size, hydrophilicity, intercellular adhesiveness, and efflux transporters, particularly, in the brain capillary endothelial cells. Drug delivery into the brain is blocked by the blood-brain barrier (BBB). Thus, developing drugs for the central nervous system (CNS) diseases remains a challenge. The approach based on receptor-mediated transcytosis (RMT) can overcome this impassable problem at the BBB. Well-designed molecules for RMT form conjugates with the ligand and drugs via linkers or nanoparticles. Cell penetrating peptides (CPPs), receptor-targeting peptides, and monoclonal antibodies (mAbs) are often used as ligands. The binding of ligand to the receptor on the endothelial cell surface induces endocytosis. Existing exosomes comprising the conjugates move in the cytoplasm and fuse with the opposite plasma membrane to release them. Subsequently, the transcytosed conjugate-loaded drugs or released drugs from the conjugates elicit activity in the brain. As receptors, transferrin receptor (TfR), low-densi...
Source: Chemical and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Chem Pharm Bull (Tokyo) Source Type: research