Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis

Marianna Carone, Marianne R. Spalinger, Robert A. Gaultney, Raffaele Mezzenga, Kristýna Hlavačková, Aart Mookhoek, Philippe Krebs (), Gerhard Rogler (), Paola Luciani () and Simone Aleandri ()
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Marianna Carone: University of Bern
Marianne R. Spalinger: University Hospital Zurich, University of Zurich
Robert A. Gaultney: University of Bern
Raffaele Mezzenga: ETH Zurich
Kristýna Hlavačková: University of Bern
Aart Mookhoek: University of Bern
Philippe Krebs: University of Bern
Gerhard Rogler: University Hospital Zurich, University of Zurich
Paola Luciani: University of Bern
Simone Aleandri: University of Bern

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Ulcerative colitis is a chronic inflammatory bowel disease that strongly affects patient quality of life. Side effects of current therapies necessitate new treatment strategies that maximise the drug concentration at the site of inflammation, while minimizing systemic exposure. Capitalizing on the biocompatible and biodegradable structure of lipid mesophases, we present a temperature-triggered in situ forming lipid gel for topical treatment of colitis. We show that the gel is versatile and can host and release drugs of different polarities, including tofacitinib and tacrolimus, in a sustained manner. Further, we demonstrate its adherence to the colonic wall for at least 6 h, thus preventing leakage and improving drug bioavailability. Importantly, we find that loading known colitis treatment drugs into the temperature-triggered gel improves animal health in two mouse models of acute colitis. Overall, our temperature-triggered gel may prove beneficial in ameliorating colitis and decreasing adverse effects associated with systemic application of immunosuppressive treatments.

Date: 2023
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DOI: 10.1038/s41467-023-39013-3

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