Thermosensitive polymer hydrogel as a physical shield on colonic mucosa for colitis treatment

Abstract

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC), is a chronic disease characterized by diffuse mucosal inflammation limited to the colon. Topical drug delivery systems that could be facilely performed and efficiently retained at colon sites are attractive for clinical IBD treatment. Herein, we report the exploration of an injectable thermosensitive copolymer hydrogel as a topical formulation for IBD treatment and demonstrate its feasibility in UC treatment by shielding ulcer sites from the external environment and being a drug reservoir for sustained release. Poly(aliphatic ester)-based triblock copolymer, poly(DL-lactic acid)–poly(ethylene glycol)–poly(DL-lactic acid) (PDLLA–PEG–PDLLA), adopts the solution state at room temperature yet a gel state at body temperature when the polymer concentration is more than 11%. The gel acts not only as a physical mucosal barrier for protecting ulcer sites from microorganisms like bacteria but also as a mesalazine depot for enhanced drug retention in the colon for localized, sustained drug release. In vivo UC treatment reveals that blank gel as a mucosal protector shows nearly the same treatment effect to mesalazine SR granules. Mesalazine-loaded gel significantly suppresses inflammation and has the best outcomes of indices such as colonic length, mucosal injury index, pathological tissue, and inflammatory factor. The injectable thermosensitive polymer hydrogel represents a novel, robust platform for the efficient treatment of IBD by acting as a physical shield to block out the pro-inflammatory factors as well as a drug depot for enhanced drug retention and controlled delivery.