From Farm to Pharmacy: Strawberry-Enabled Oral Delivery of Protein Drugs release_52h5zd3virep5jfcxxwpe7d6vi

by Nicholas G. Lamson, Katherine C. Fein, John P. Gleeson, Sijie Xian, Alexandra Newby, Namit Chaudhary, Jilian R. Melamed, Kyle Cochran, Rebecca L. Ball, Kanika Suri, Vishal Ahuja, Anna Zhang (+5 others)

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Although oral drug delivery is preferred by patients, it is not possible for proteins because the gastrointestinal tract is not sufficiently permeable. To enable the non-toxic oral uptake of protein drugs, we investigated plant-based foods as intestinal permeation enhancers, hypothesizing that compounds found in food would be well-tolerated by the gastrointestinal tract. Following a screen of over 100 fruits, vegetables, herbs, and fungi, we identified strawberry as a potent enhancer of macromolecular permeability in vitro and in mice. Natural product chemistry techniques identified pelargonidin, an anthocyanidin, as the active compound. In mice, insulin was orally administered with pelargonidin to induce sustained pharmacodynamic effects with doses as low as 1 U/kg and bioactivity of over 100% relative to the current gold standard of subcutaneous injection. Pelargonidin-induced permeability was reversible within two hours of treatment, and one month of daily dosing did not adversely affect mice as determined by weight tracking, serum concentrations of inflammatory markers, and tight junction gene expression. Results underscore the utility of plant-based foods in biomedical applications and demonstrate pelargonidin as an especially potent enhancer for the oral delivery of biologics.
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