A sticky situation helps colitis

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Science Translational Medicine  22 Apr 2015:
Vol. 7, Issue 284, pp. 284ec67
DOI: 10.1126/scitranslmed.aab3130

Inflammatory bowel disease—in particular, ulcerative colitis—is often treated with topical, rectally administered therapies—which deliver a high concentration of active drug to injured tissue. But such topical therapies can be difficult for patients, who may be actively experiencing diarrhea and urgency and for whom enema retention can therefore be particularly challenging. Now, Sinha and colleagues described a new drug delivery system that allows for better retention of active drugs in the colon.

Sinha et al. have created a liquid that phase-transitions to a gel at body temperature. They used polypropylene and polyethylene block copolymers to find optimal formulations with a liquid-gel transition at near body temperature. By loading barium sulfate into their formulations and using micro-CT and serial volumetric evaluations, the authors demonstrated that this temperature-sensitive drug delivery system improved colonic retention time and retrograde propagation distance in both healthy mice and a mouse model of colitis. Both budesonide and mesalamine improved histological disease scores and other markers of disease. In a second colitis mouse model, positive outcomes were observed with budesonide. The rectal administration of a formulation that transitions to a semisolid could raise concern about gastrointestinal obstruction, but mice that develop intestinal strictures reassuringly showed no increase in tendency toward bowel block.

This innovative formulation allows the drug to linger longer in the colon and could broaden the number of therapeutics that can be delivered through the gastrointestinal tract and enhance the diffusion of drugs into inflamed mucosa. As the authors point out, adapting this technology to facilitate the delivery of biologics through the gut could be of substantial benefit to patients.

S. R. Sinha et al., A thermo-sensitive delivery platform for topical administration of inflammatory bowel disease therapies. Gastroenterology 10.1053/j.gastro.2015.04.002 (2015). [Abstract]

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