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Identification of Targeting Peptides for Mucosal Delivery in Sheep and Mice

Kenngott et al., Molecular Pharmaceutics (2015) - PMID: 26568284

Product(s) used in this publication:  Custom Peptide Synthesis

Abstract:

In this study we identified and characterized a novel cyclic peptide that facilitates the rapid transportation of conjugated molecules across the epithelial layer of the small intestine. The peptide was initially selected from phage display libraries using a large animal experimental model, which employed consecutive in vitro and in vivo panning. The procedure was designed to enrich for peptides that facilitated transcytosis across the intestinal epithelium into the intestinal afferent lymphatic system. A small set of peptides was repeatedly isolated using this selection method; however, the cyclic nonamer CTANSSAQC, 13C, dominated. The activity of the putative targeting peptide 13C was then verified using a mouse model. These experiments showed that the 13C peptide as well as macromolecules conjugated to it were rapidly transported across the intestinal mucosa into distinct subsets of epithelial cells and CD11c+ cells located in the lamina propria and Peyer's Patches. Significant amounts of intact protein could be delivered into the systemic circulation after rectal and nasal application. Thus, peptide 13C is regarded as an attractive carrier candidate for mucosal delivery of large molecules. The preferential targeting to distinct intestinal cells may be utilized to deliver active biological drugs for the effective control of diseases of the gut.

KEYWORDS:

lymphatic cannulation; mucosal uptake; phage display; protein delivery; sheep; transcytosis

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