Enhancing β‐carotene bioavailability and protective effects for dextran sodium sulfate‐induced colitis with sesame protein hydrolysate nanoparticles

Abstract Background Inflammatory bowel disease (IBD) is a chronic condition marked by recurring intestinal inflammation, leading to symptoms such as fatigue, diarrhea, and weight loss. Current treatments are limited, highlighting the need for new therapeutic strategies. β‐Carotene (BC), a natural antioxidant, has potential in managing colitis, but its low bioavailability limits its efficacy. This study evaluated a novel BC‐loaded sesame protein hydrolysate nanoparticles (BC‐SPH NPs) formulation to enhance BC bioavailability and therapeutic performance in a dextran sodium sulfate (DSS)‐induced colitis model. Results BC‐SPH NPs showed an average size of 50.30 ± 0.43 nm, an encapsulation efficiency of 75.23 ± 0.92%, a prolonged plasma residence profile, with a time to reach maximum plasma concentration ( T max ) of 8 h, and a peak plasma concentration of 64.982 ng mL −1 . Notably, the NPs enabled enhanced tissue distribution of BC to key tissues in rats including kidneys, liver, small intestine, and colon. In DSS‐induced colitis mice, BC‐SPH NPs significantly reduced disease activity index, improved body weight, preserved colon length and structure, and prevented inflammatory cell infiltration. Additionally, BC‐SPH NPs lowered serum interleukin‐6 (IL‐6), interleukin‐1β (IL‐1β), and tumor necrosis factor alpha (TNF‐α), as well as colonic myeloperoxidase (MPO) activity and nitric oxide (NO) levels. Furthermore, BC‐SPH NPs up‐regulated tight junction proteins Claudin‐1, ZO‐1, and Occludin, indicating improved intestinal barrier integrity. In contrast, free BC provided only modest effects. Conclusion This study demonstrates that BC‐SPH NPs substantially enhance the bioavailability and therapeutic effects of BC in DSS‐induced colitis compared to free BC. The nanoformulation effectively alleviates colitis symptoms, preserves intestinal integrity, and reduces inflammation, suggesting that BC‐SPH NPs represent a promising natural therapeutic option for the prevention and treatment of ulcerative colitis. © 2025 Society of Chemical Industry.