Self-Assembly of Anti-Inflammatory Peptide Amphiphiles for Mucosal Health

Authors

• Maria José Gómara, Unit of Synthesis and Biomedical Applications of Peptides, Institute of Advanced Chemistry of Catalonia (IQAC-CSIC)
• Ignacio Pérez-Pomeda, Cell Culture Service, Centro de Investigación y Desarrollo
• Ramon Pons, Institute of Advanced Chemistry of Catalonia
• Paul Ziprin, Imperial College London
• Carolina Herrera, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Isabel Haro, Unit of Synthesis and Biomedical Applications of Peptides, Institute of Advanced Chemistry of Catalonia (IQAC-CSIC)

Document Type

Article

Publication Date

2026

DOI

10.1002/cbic.202500929

Publication Title

ChemBioChem

Volume

27

Issue

7

Pages

e202500929

Abstract

Broad spectrum anti-inflammatory peptide amphiphiles (AIF-PAs) have been developed as an innovative strategy for the treatment of chronic mucosal inflammation and the prevention of HIV transmission. Novel lipopeptides based on two linear sequences of anti-inflammatory peptides were obtained by solid-phase peptide chemistry. In a pilot study, ex vivo exposure of colorectal tissue explants from Crohn's disease patients to AIF-PAs induced a downregulation of the proinflammatory profile. Furthermore, the HIV inhibitory potency of AIF-PAs was evaluated ex vivo in colorectal tissue explants, obtaining sub-micromolar IC₅₀ values. Characterization of AIF-PAs self-aggregation in aqueous solution revealed that the net charge distribution within the peptides influenced their conformation in water and their self-assembly into larger structures. AIF-PAs with neutral net charge displayed a β-sheet conformation, whereas AIF-PAs with positive net charge were characterized by a random coil conformation. The morphology of the nanostructures fully correlated with the peptide secondary structure and self-aggregation levels. Interactions with model membranes and epithelial cells demonstrated that the cationic charge and amphiphilic nature of self-assembled AIF-PAs facilitated their binding and localization to lipid bilayers and cell membranes. Finally, AIF-PAs were unable to cross epithelial cell monolayers in permeability assays, indicating a low mucosal permeation potential. Their lack of permeation reduces systemic absorption, thus concentrating and retaining the bioactive peptides at the mucosal surface, where local activity is desired. In summary, peptide-based therapies leverage the beneficial anti-inflammatory properties of peptides, combined with amphiphilic structures that allow precise targeting and improved delivery to mucosal tissues.

Rights

© 2026 The Authors

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Data Availability

Article states: "The data that support the findings of this study are available from the corresponding author upon reasonable request."

Original Publication Citation

Gómara, M. J., Pérez-Pomeda, I., Pons, R., Ziprin, P., Herrera, C., & Haro, I. (2026). Self-assembly of anti-inflammatory peptide amphiphiles for mucosal health. ChemBioChem, 27(7), Article e202500929. https://doi.org/10.1002/cbic.202500929

Repository Citation

Gómara, M. J., Pérez-Pomeda, I., Pons, R., Ziprin, P., Herrera, C., & Haro, I. (2026). Self-assembly of anti-inflammatory peptide amphiphiles for mucosal health. ChemBioChem, 27(7), Article e202500929. https://doi.org/10.1002/cbic.202500929