Bioengineered curcumin-SCFA co-loaded PLGA nanoparticles for modulating inflammation and epithelial barrier integrity in radiation-induced enteritis

Radiation enteritis (RE) is a common side effect of abdominal radiotherapy, which causes intestinal inflammation and impairment of epithelial barrier. In this study, we developed a bioengineered dual-delivery nanosystem by encapsulating curcumin and microbiota-derived short-chain fatty acids (SCFAs: acetate, propionate, and butyrate) into PLGA nanoparticles (Cur-PLGA NPs@SCFAs). The formulation encapsulated 66% of curcumin and released it slowly over 48 h, with about 72.6% of it being released at pH 7.4. In vitro studies using Caco-2 cells, the Cur-PLGA NPs@SCFAs maintained good cytocompatibility, with cell viability over 81.5% at 40 µg/mL as well as reduced intracellular reactive oxygen species to 65.1% of control levels. Wound closure reached 86.2% at 48 h whereas compared to untreated cells (42.7%). In vivo mice model, high-dose administration (40 mg/kg) markedly improved disease outcomes, reducing the Disease Activity Index to 3.8 ± 0.4 compared with 8.6 ± 0.5 in the RE group, while restoring colon length (7.1 ± 0.2 cm) and spleen index (0.29 ± 0.01%). Pro-inflammatory mediators IL-6 and TNF-α were decreased, accompanied by suppression of NF-κB p65 signaling, whereas IL-10 and the tight junction proteins ZO-1 and occludin were increased. Antioxidant defenses (GSH, SOD, and T-AOC) were recovered, and cecal SCFA levels were nearly doubled, collectively indicating a protective effect on intestinal inflammation and barrier integrity.