Basics and Recent Advances in Peptide and Protein Drug Delivery

TLDR

Peptide and protein therapeutics have expanded rapidly, yet their clinical use remains constrained by delivery challenges, as oral administration is hampered by gastrointestinal degradation and limited absorption, transdermal routes avoid the gut but face absorption barriers, and free peptides lack systemic stability due to proteases, opsonization, and agglutination. The review aims to examine oral and transdermal peptide drug delivery, highlighting barriers and solutions to absorption and stability challenges. The authors review strategies such as absorption enhancers, enzyme inhibitors, carrier systems, stability enhancers, and methods to boost systemic stability and achieve site‑specific delivery.

Abstract

While the peptide and protein therapeutic market has developed significantly in the past decades, delivery has limited their use. Although oral delivery is preferred, most are currently delivered intravenously or subcutaneously due to degradation and limited absorption in the gastrointestinal tract. Therefore, absorption enhancers, enzyme inhibitors, carrier systems and stability enhancers are being studied to facilitate oral peptide delivery. Additionally, transdermal peptide delivery avoids the issues of the gastrointestinal tract, but also faces absorption limitations. Due to proteases, opsonization and agglutination, free peptides are not systemically stable without modifications. This review discusses oral and transdermal peptide drug delivery, focusing on barriers and solutions to absorption and stability issues. Methods to increase systemic stability and site-specific delivery are also discussed.