Polydopamine-encapsulated modified Pulsatilla decoction: a strategy to enhance ulcerative colitis therapy

In Traditional Chinese Medicine (TCM), ulcerative colitis (UC) is often categorized as "protracted dysentery." Pulsatilla Decoction has been reported to exert therapeutic benefits in patients with protracted dysentery. To potentially improve therapeutic outcomes in ulcerative colitis, we prepared a modified Pulsatilla Decoction (MPD). Preliminary clinical observations have suggested that MPD may alleviate symptoms in UC patients. However, rectal enema of MPD is often limited by suboptimal patient compliance and relatively short colonic retention. These limitations underscore the need for new TCM formulations. In this study, we encapsulated MPD within polydopamine (PDA) nanoparticles to prolong colonic residence and evaluate therapeutic effects in a UC model.

First, PDA@MPD was prepared by encapsulating MPD with PDA. Fourier transform infrared spectroscopy (FT-IR) and other analytical instruments characterized its structure, morphology, and particle size. Drug release property was evaluated by UV-vis spectrophotometry. Subsequently, MPD active components were labeled with Fluorescein isothiocyanate (FITC); PDA@FITC-MPD was prepared similarly and administered orally to mice. In vivo fluorescence imaging tracked retention time and location in the gastrointestinal tract. Finally, the UC model was induced with 3% DSS. After 7 days of PDA@MPD treatment, therapeutic efficacy was assessed via disease activity index (DAI), colon length, histopathology, Western blot, quantitative real-time PCR (qRT-PCR), and ELISA.

MPD was encapsulated by PDA. Relative to MPD, PDA@MPD showed a prolonged colonic retention time and modest improvements in colonic damage scores and inflammatory markers in DSS-induced UC mice. These changes were associated with up-regulation of tight-junction proteins (Occludin, ZO-1) and down-regulation of pro-inflammatory cytokines (IL-1β, TNF-α) in the PDA@MPD group.

This study indicates that PDA@MPD prolongs colonic retention and is associated with modest improvements in DSS-induced colonic damage and inflammation in mice. These findings may offer a proof-of-concept for exploring polydopamine-based delivery systems in TCM formulations.