Biotin-modified starch nanoparticles for resveratrol delivery: Encapsulation mechanism and synergistic efficacy in ulcerative colitis therapy

Resveratrol (RES) is a promising anti-inflammatory polyphenol for treating ulcerative colitis (UC), but its efficacy is constrained by poor solubility and colon-targeting efficiency. Biotin, as an active ligand, has been widely used to functionalize nanocarriers to enhance intestinal cell permeability, thereby increasing the absorption of bioactive components. Biotin modification enlarged the helical cavity of starch into a V7-type structure, creating a more favorable hydrophobic microenvironment for the encapsulation of guest molecules. The mass ratio of resveratrol to starch was 1:10 to 1:2, resveratrol acted as a nucleator, forming ordered B+V crystals with minimal size (312.4 nm), uniform distribution, and high encapsulation (20.02 %). Excess resveratrol distorted helices, causing aggregation and reduced efficiency. Biotin modification facilitating nanoparticles uptake by Caco-2 via receptor-mediated endocytosis. Furthermore, the colon length of colitis mice treated with resveratrol-loaded BSNP increased by 25 % ( P  < 0.001) compared to that of untreated colitis mice. RES@BSNP can increase the relative abundance of beneficial gut microbiota such as Christensenellales and Lactobacillus and suppressing pro-inflammatory factor secretion, ultimately alleviating UC. This work elucidates the role of guest-molecule concentration and biotin functionalization in starch-based nanoparticle design, offering a promising strategy for targeted polyphenol delivery in colitis treatment.