Berberine hydrochloride sustained-release solid dispersion alleviates acetic acid-induced ulcerative colitis in rats by modulating intestinal flora

Berberine hydrochloride (BH) is a natural alkaloid compound known for its effectiveness in treating ulcerative colitis (UC). However, the clinical application of BH was limited due to the short half-life and rapid metabolism in body. Therefore, a sustained-release solid dispersion (SD) of BH was prepared using different proportions of ethyl cellulose as carrier. PXRD, DSC, and FT-IR analyses confirmed the transition of BH from a crystalline to amorphous state. This transformation significantly improved the drug release rate of BH and the pharmacokinetic characteristics in rats. The in vitro dissolution results showed that the cumulative dissolution rates of SD (1:4) were 29.47 % and 93.88 % at 10 min and 24 h respectively, and the in vivo study demonstrated that the t 1/2 (0−24) and the AUC 0−24 of SD (1:4) were 5.52 times and 6.30 times greater than those of BH, respectively, indicating SD (1:4) superior sustained-release effect compared to BH. In the acetic acid (AA)-induced UC rat model, SD treatment alleviates UC by increasing colon length, improving pathological damage, and reducing both the DAI score and levels of inflammatory factors. The 16S rRNA sequencing results indicated that SD treatment reshaped gut microbiota in rats with UC, particularly increasing the abundance of probiotic Romboutsia and decreasing the abundance of pathogenic bacteria Erysipelotrichaceae , Clostridia_UCG_014 and Dubosiella . In conclusion, we successfully prepared a sustained-release SD of BH and demonstrated that its therapeutic effect on UC is achieved by regulating intestinal microbiota.