Efficiency of a novel thermosensitive enema in situ hydrogel carrying Periplaneta americana extracts for the treatment of ulcerative colitis.

The aim of this study was to develop a thermosensitive gel (TISG) as an effective rectal delivery platform for delivering extracts (PA) to alleviate ulcerative colitis (UC) and explore the underlying molecular mechanism. Thermosensitive (poloxamer 407) and adhesive polymers (chondroitin sulfate modified carboxymethyl chitosan, CCMTS) were used to construct the gel. CCMTS and aldehyde poloxamer 407 (P407-CHO) were synthesized and chemically cross-linked by Schiff base reaction to formulate thermosensitive gel, which carried extracts (PA/CCMTS-P). The cytotoxicity and cellular uptake of CCMTS-P were investigated in lipopolysaccharide (LPS) -induced macrophages by CCK-8 assay. The anti-inflammatory effects of PA/CCMTS-P were studied in lipopolysaccharide-induced RAW264.7 cells and dextran sulfate sodium (DSS)-induced ulcerative colitis mouse models. In addition, the ability of PA/CCMTS-P to restore the intestinal mucosal barrier after rectal administration was evaluated by immunohistochemical analysis (IHC). PA/CCMTS-P was prepared and characterized as gel with a phase-transition temperature of 32.9°C. The results of the experiments indicated that the hydrogels promoted the cellular uptake of extracts without causing any toxicity as compared to the free gel. PA/CCMTS-P showed superior anti-inflammatory activity both and which restored the damaged intestinal mucosal barrier associated by inhibiting necroptosis in dextran sulfate sodium-induced ulcerative colitis models. The findings from our study show that the rectal administration of PA/CCMTS-P holds a promising potential for the treatment of ulcerative colitis.