Improving Trans-Mucosal Delivery of Peptides and Proteins by Carrier-Peptide Coupling

Mucosal delivery of macromolecular drugs or antigenic material across the intestinal epithelium still remains a major challenge in drug development. However, efficient mucosal transport is essential for immune modulation in the small intestine. Therefore we investigated the potential of a newly discovered carrier peptide, namely the 13C-peptide. Immunohistochemical analysis of small intestinal tissue after injection of fluorochrome coupled 13C-peptide revealed enhanced peptide uptake by epithelial cells. Furthermore, application of 13C coupled peptide led to an efficient systemic distribution. To investigate the potential of 13C-peptide to enhance the intestinal transcytosis of coupled proteins, the model protein streptavidin was conjugated to 13C or a scrambled control peptide. While 13C-streptavidin was very efficiently taken up by small intestinal epithelial cells, streptavidin conjugated to the scrambled control peptide was not transported across the mucosa. Interestingly, 13C-protein construct was not only detected inside epithelial cells, but could also be visualized in CD11c positive cells in the villi as well as in Peyers Patches, suggesting that dendritc cells play a major role in the transport mechanism. As a next step we plan to conjugate anti-inflammatory cytokines to 13C-peptide to specifically target the inflammed intestinal mucosa. We believe that local treatment with 13C coupled cytokines can be a promising therapeutic tool in the treatment of inflammatory bowel diesase (IBD).