Peptide-Enhanced Cargo Transport across 2D and 3D Epithelial Barriers: A Structure-Function Investigation

Abstract

There is a great need to enhance the delivery of therapeutics across biological barriers, such as the blood-brain barrier. We have identified a cationic peptide, called the CL peptide, which can deliver a small-molecule cargo across a 2D epithelial barrier model at a moderately high rate. In this study, we measure cargo delivery in a novel 3D microvessel platform. Furthermore, we investigate the effect of arginine spacing, number of arginines, secondary structure, stereochemistry, and other parameters on the cargo permeability. These studies can help provide design rules for developing novel peptides for transcellular cargo delivery.