Cell-penetrating peptides for transmucosal delivery of proteins

J Control Release. 2024 Feb:366:864-878. doi: 10.1016/j.jconrel.2024.01.038. Epub 2024 Jan 27.

Abstract

Enabling non-invasive delivery of proteins across the mucosal barriers promises improved patient compliance and therapeutic efficacies. Cell-penetrating peptides (CPPs) are emerging as a promising and versatile tool to enhance protein and peptide permeation across various mucosal barriers. This review examines the structural and physicochemical attributes of the nasal, buccal, sublingual, and oral mucosa that hamper macromolecular delivery. Recent development of CPPs for overcoming those mucosal barriers for protein delivery is summarized and analyzed. Perspectives regarding current challenges and future research directions towards improving non-invasive transmucosal delivery of macromolecules for ultimate clinical translation are discussed.

Keywords: Buccal and sublingual; Cell-penetrating peptides (CPPs); Intranasal; Oral; Peptides; Proteins; Transmucosal delivery.

Publication types

  • Review

MeSH terms

  • Administration, Mucosal
  • Cell-Penetrating Peptides* / chemistry
  • Drug Delivery Systems
  • Humans
  • Mouth Mucosa / metabolism
  • Proteins / metabolism

Substances

  • Cell-Penetrating Peptides
  • Proteins