Lactose-decorated, alginate-coated chitosan nanoparticles loaded with Coomassie Brilliant Blue G-250 protect colonic barrier integrity in experimental colitis.

Ulcerative colitis involves epithelial injury, crypt distortion, barrier failure, and inflammatory activation within colonic tissue. To support local delivery of the P2X7R antagonist Coomassie Brilliant Blue G-250 (BBG), we developed lactose-decorated, alginate-coated chitosan nanoparticles (ALG-BBG-LCS NPs) and evaluated whether this dual-modified polysaccharide carrier could decouple colonic exposure from systemic exposure while translating into structural protection in dextran sodium sulfate-induced colitis. Lactosylated chitosan was synthesized by the Maillard reaction and confirmed by 1H NMR, FTIR, and substitution-degree analysis. BBG-loaded nanoparticles were prepared by ionic gelation, coated with alginate, and characterized for size, surface charge, entrapment-efficiency, morphology, and pH-sequential release. ALG-BBG-LCS NPs formed spherical nanoparticles (255.16 ± 2.75 nm) with negative surface charge (-22.1 ± 1.31 mV), entrapment-efficiency of 76.57 ± 0.48%, and markedly reduced pre-colonic BBG release. In colitic rats, the optimized formulation produced the highest colonic exposure with the lowest systemic exposure, highlighting the ability of this dual-modified nanocarrier to preferentially localize BBG to the diseased colon while limiting off-target distribution. More importantly, it attenuated disease activity and preserved tissue organization, as shown by improved macroscopic appearance, reduced histologic injury, lower nuclear phospho-NF-κB p65 immunostaining, and restoration of ZO-1 and Occludin expression. These structural improvements were accompanied by suppression of the colonic P2X7R/NF-κB/NLRP3/caspase-1 axis, reduced cytokine and oxidative injury, and improved barrier-function indices. Overall, ALG-BBG-LCS NPs provide a colon-directed BBG platform whose significance extends beyond drug delivery to decoupling colonic drug exposure from systemic exposure and thereby promoting preservation of colonic tissue architecture and epithelial barrier integrity in experimental colitis.