Constraint of Lignin–Carbohydrate Complex Orchestrated on Polyphenol in Oil–Water Interface Targeting Ulcerative Colitis Therapy

Qian Wu; Xingyu Zhang; Jingjia Zhang; Gaohui Huang; Chen Zhou; Chunlin Li; Xiaojun Huang; Jianbo Xiao; Nianjie Feng; Yuanbin She

Resumen:

The therapeutic potential of polyphenols in ulcerative colitis (UC), mediated through immune modulation and gut microbiota homeostasis. To enhance the oral bioavailability of polyphenols, we architected a colon–targeted W1/O/W2 emulsion system featuring a rationally designed lignin–carbohydrate complex (LCC) as a dual–functional emulsifier system for the first time. Based on the innate structural duality of LCC, which comprising hydrophobic lignin and hydrophilic carbohydrates, we employed LCC for O/W emulsifier. This inherent amphiphilicity was further engineered via laccase–mediated grafting of isovanillin, yielding a modified LCC with tailored lipophilicity for effective W/O interfacial stabilization. The W1/O/W2 emulsion ensured the stability of the encapsulated polyphenols with divergent polarity but also enabled pH–responsive payload release under colonic conditions (pH >7.0). In DSS–induced colitis, the system demonstrated a synergistic effect, the LCC itself acted as a prebiotic to modulate the gut microbiota, specifically enriching short chain fatty acid–producing bacteria, while the released polyphenols reinforced the intestinal barrier, which collectively accelerated mucosal healing. This research proposes a carbon–neutral therapeutic strategy for colitis, not only establishing a proof–of–concept for replacing synthetic emulsifiers with engineered biomass, but also as a multi–functional platform to stabilize colon–targeted co–delivery system and microbiome regulation in colitis.