Cell-penetrating peptides for transmucosal delivery of proteins

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 revi...

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Bibliographic Details
Published in:Journal of controlled release 2024-02, Vol.366, p.864-878
Main Authors: Wu, Jiamin, Roesger, Sophie, Jones, Natalie, Hu, Che-Ming J., Li, Shyh-Dar
Format: Article
Language:English
Subjects:
Buccal and sublingual
Cell-penetrating peptides (CPPs)
Intranasal
Oral
Peptides
Proteins
Transmucosal delivery
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Summary: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. [Display omitted] •Cell-penetrating peptides (CPPs) enhance biological drug permeation across various mucosal barriers.•CPPs use endocytosis, direct translocation, and membrane destabilization to mediate intracellular transport.•Local administration of CPPs is a preferable route with clinical successes.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2024.01.038