Oral colon-targeted paeonol emulsion for ameliorating ulcerative colitis based on charge adsorption.

Ulcerative colitis (UC), an inflammatory bowel disease, poses a severe threat to human health. Paeonol has demonstrated potential for the treatment of UC, particularly because of its remarkable anti-inflammatory properties. However, the high volatility and low oral bioavailability of paeonol hinder its application in the treatment of UC. To address this challenge, a paeonol emulsion (PEM)-based oral delivery system was developed for the treatment of UC. In this study, we investigated the colonic-targeting efficacy of PEM and the mechanisms underlying its ability to alleviate colitis. The results revealed that the negatively charged PEM specifically adhered to the positively charged inflamed colonic tissues via electrostatic interactions, enabling effective targeted delivery. Additionally, the PEM maintained the balance between M1 and M2 macrophages, exhibiting excellent efficacy in alleviating UC. Mechanistic studies have shown that PEM significantly inhibits the expression of inflammatory cytokines and repairs the intestinal barrier. Furthermore, PEM modulates the composition of the gut microbiota by inhibiting the growth of harmful bacteria and promoting the growth of beneficial bacteria. In conclusion, the negatively charged emulsion delivery system constructed provides new insights into the development of an oral colon-targeted drug delivery system.