Characterization and impact of peptide physicochemical properties on oral and subcutaneous delivery

Peptides, an emerging modality within the biopharmaceutical industry, are often delivered subcutaneously with evolving prospects on oral delivery. Barrier biology within the subcutis or gastrointestinal tract is a significant challenge in limiting absorption or otherwise disrupting peptide disposition. Aspects of peptide pharmacokinetic performance and ADME can be mitigated with careful molecular design that tailors for properties such as effective size, hydrophobicity, net charge, proteolytic stability, and albumin binding. In this review, we endeavor to highlight effective techniques in qualifying physicochemical properties of peptides and discuss advancements of in vitro models of subcutaneous and oral delivery. Additionally, we will delineate empirical findings around the relationship of these physicochemical properties and in vivo (animal or human) impact. We conclude that robust peptide characterization methods and in vitro techniques with demonstrated correlations to in vivo data are key routines to incorporate in the drug discovery and development to improve the probability of technical and commercial success of peptide therapeutics. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

Peptides are an emerging modality in the biopharmaceutical industry, with subcutaneous delivery being the main route, but oral delivery is also being developed. However, barrier biology in subcutaneous tissue or the gastrointestinal tract can limit absorption of peptides, so careful molecular design is needed to optimize their properties. This review highlights effective techniques for evaluating the physicochemical properties of peptides and discusses the use of in vitro models in subcutaneous and oral delivery.