AUTHOR=Wu Ming , Ding Hui , Tang Xiao , Chen Jiayi , Zhang Meng , Yang Ziqiong , Du Qian , Wang Jun 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1111267

DOI=10.3389/fphar.2023.1111267

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> The aim of this study was to develop a thermosensitive <italic>in situ</italic> gel (TISG) as an effective rectal delivery platform for delivering <italic>Periplaneta americana</italic> extracts (PA) to alleviate ulcerative colitis (UC) and explore the underlying molecular mechanism.</p><p><bold>Materials and methods:</bold> Thermosensitive (poloxamer 407) and adhesive polymers (chondroitin sulfate modified carboxymethyl chitosan, CCMTS) were used to construct the <italic>in situ</italic> gel. CCMTS and aldehyde poloxamer 407 (P407-CHO) were synthesized and chemically cross-linked by Schiff base reaction to formulate thermosensitive <italic>in situ</italic> gel, which carried <italic>Periplaneta americana</italic> 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).</p><p><bold>Results:</bold> PA/CCMTS-P was prepared and characterized as gel with a phase-transition temperature of 32.9°C. The results of the <italic>in vitro</italic> experiments indicated that the hydrogels promoted the cellular uptake of <italic>Periplaneta americana</italic> extracts without causing any toxicity as compared to the free gel. PA/CCMTS-P showed superior anti-inflammatory activity both <italic>in vitro</italic> and <italic>in vivo,</italic> which restored the damaged intestinal mucosal barrier associated by inhibiting necroptosis in dextran sulfate sodium-induced ulcerative colitis models.</p><p><bold>Conclusion:</bold> The findings from our study show that the rectal administration of PA/CCMTS-P holds a promising potential for the treatment of ulcerative colitis.</p>