Advanced targeted curcumin delivery using biodegradable hierarchical microspheres with calcium pectinate matrix and hyaluronic acid moieties for enhancing colitis amelioration.

Oral targeted delivery systems for food bioactive compounds have attracted considerable attention for improving the efficiency of nutritional interventions. In this study, a hierarchical curcumin carrier with sequence-targeting capability was fabricated to mitigate colitis through a convenient and environmentally friendly approach. Initially, curcumin-loaded nanostructured lipid carriers (NLC) with hyaluronic acid (HA) moieties (HA-NLC) were prepared using ovalbumin-HA conjugates as emulsifiers. Subsequently, HA-NLC was immobilized within a calcium pectinate matrix using electrospray, leading to the formation of supramolecular microspheres (HA-NLC@MPs) approximately 140 μm in size. Results suggested that the pectin matrix preserved the integrity of the carrier and prevented curcumin leakage during transit through the upper gastrointestinal tract, while selectively degrading in response to colon bacteria. Moreover, the exposed HA moieties on the released HA-NLC facilitated the transcellular absorption of curcumin by inflamed colonic enterocytes through cluster of differentiation-44 receptor-mediated endocytosis. In vitro and in vivo studies demonstrated predominant curcumin accumulation in the colorectal tissues of colitis mice using HA-NLC@MPs as carrier. Curcumin delivered via HA-NLC@MPs demonstrated superior effects in alleviating colitis compared with that in the nanocarriers, through the modulation of macrophage polarization, TLR4/MyD88/NF-κB signaling cascade, and gut microbiota homeostasis.