Oral administration of polyelectrolyte modified curcumin-loaded egg protein nanoparticles for suppression of inflammation in colitis mice.

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease affecting the large intestine, resulting in inflammation to the mucosa and submucosa of the colon. Overproduction of reactive oxygen species (ROS) plays an important role in contributing to the exacerbation of inflammation and strategies aimed at reducing ROS in the inflamed colon offer potential therapeutic benefits for managing UC. Curcumin possesses antioxidant and anti-inflammatory effects; however, it faces many challenges, such as rapid metabolism and low solubility. In this study, we developed a curcumin-loaded egg protein nanoparticle (Cur@EPN(P)) coating with a polyion complex of N,N,N trimethyl chitosan (TMC) and sodium alginate (SA). Egg protein nanoparticle significantly enhanced the solubility and antioxidant activity of curcumin, and a polyelectrolyte layer composed of TMC and SA improved the stability of nanoparticles and controlled drug release under gastrointestinal conditions. The Cur@EPN(P) exhibited an approximate diameter of 243.5 ± 7.3 nm with the pH dependent surface charge. In vitro evaluation, Cur@EPN(P) significantly increased antioxidant and anti-inflammatory properties by scavenging ABTS and hydroxyl radicals and reducing nitric oxide levels in lipopolysaccharide-activated RAW 264.7 macrophage cells. In vivo pharmacokinetic study, mice treated with orally administered Cur@EPN(P) showed a greater accumulation of curcumin in the colon tissues as compared to free curcumin treatment. The therapeutic effect of Cur@EPN(P) showed an improvement in colon length and a reduction in colonic tissue damage in colitis mice model by effectively suppressing the inflammatory and oxidative molecules. In conclusion, Cur@EPN(P) may serve as a potential orally administered nanomedicine for the anti-inflammatory management of UC.