Colon-targeted self-assembled nanoparticles loaded with berberine double salt ameliorate ulcerative colitis by improving intestinal mucosal barrier and gut microbiota
Abstract
Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease marked by disturbances in intestinal mucosal barriers, persistent inflammation, oxidative stress, and dysbiosis of the intestinal microbiota. Traditional treatments often fail to adequately address these issues, primarily targeting inflammation. To address these limitations, this study developed an innovative approach using self-assembled nanoparticles for oral administration that target colonic inflammation. Berberine hydrochloride and ursodeoxycholic acid were combined to form a double salt (BeU), enhancing solubility and encapsulation. An amphiphilic polymer (FU-PA) was created by esterifying fucoidan with palmitic acid. FU-PA/BeU nanoparticles were prepared using the nanoprecipitation method and further encapsulated in acid-resistant sodium alginate microspheres (FU-PA/BeU NPs@MS) for targeted delivery to colonic lesions. The aggregation rate of nanoparticles with mucus was significantly reduced to 59 % of free berberine, while the apparent permeability coefficient increased by 2.4 times. In vitro, FU-PA/BeU NPs effectively targeted inflammatory macrophages, reducing IL-6 and NO levels while increasing IL-10 level (to 42.5 %, 26.8 %, and 539 % of the LPS-treated group, respectively). Additionally, the ABTS and DPPH radical scavenging capabilities of FU-PA/BeU NPs were 177.8 % and 151.7 % of BeU, respectively. In dextran sulphate sodium-induced UC mice, oral FU-PA/BeU NPs@MS significantly improved…
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