Solid-in-oil-in-water multilayer emulsions based on programmed sequential release of resveratrol and vitamin D3 for the amelioration of ulcerative colitis

Co-administration of natural anti-inflammatory active ingredients is a prospective strategy for intervening in ulcerative colitis (UC). Resveratrol (Res) possesses synergistic efficacy with vitamin D3 (Vd) in combating UC. However, it is difficult for Vd and Res to sequentially reach the small intestine and colon after oral administration to exert their synergistic anti-colitis effects due to their poor solubility, instability, and sensitivity to the gastrointestinal environment. Herein, Res and Vd were co-encapsulated in solid-in-oil-in-water emulsions (S/O/W-E), where the aqueous phase consisted of carboxymethyl starch/propylene glycol alginate complexes, the oil phase was coconut oil, and the solid phase was carboxymethyl konjac glucomannan-coated gliadin nanoparticles. The encapsulation efficiency of Res and Vd was determined to be 95.1 % and 94.7 %, respectively. The in vitro release results confirmed that the prepared S/O/W-E not only effectively protected Res and Vd from degradation under gastric conditions but also ensured that the encapsulated Vd and Res are released sequentially in the small intestine and colon. Furthermore, co-encapsulating Res and Vd in S/O/W-E could dramatically relieve symptoms in dextran sodium sulfate-induced UC mice and ameliorate UC by regulating inflammatory cytokine expression and oxidative stress levels. The present study demonstrates that S/O/W-E with programmed sequential release is a promising delivery vehicle to alleviate colitis by combining different action modes of different anti-inflammatory active ingredients, providing new insights into the synergistic amelioration of UC.