Polydopamine-Encapsulated Modified Pulsatilla Decoction: A Strategy to Enhance Ulcerative Colitis Therapy

Background: Ulcerative colitis (UC) is classified as "protracted dysentery" in Traditional Chinese Medicine (TCM). Pulsatilla Decoction is a highly effective prescription for treating protracted dysentery. To enhance UC treatment efficacy, we innovatively modified Pulsatilla Decoction (MPD). Previous studies have confirmed MPD's therapeutic effects on UC patients. However, the common enema administration of MPD has limitations, including poor patient compliance and short drug retention time. These limitations underscore the need for new TCM formulations. In this study, we used polydopamine (PDA) nanomaterials to encapsulate MPD, aiming to increase MPD's colon retention time and improve UC treatment outcomes. Methods: First, PDA was used to encapsulate MPD, forming PDA@MPD. Fourier Transform Infrared Spectroscopy (FT-IR) and other analytical instruments were employed to characterize the structure, morphology, and particle size of PDA@MPD. Next, the drug release property of PDA@MPD was evaluated using UV-vis spectrophotometry. Subsequently, the active components of MPD were labeled with Fluorescein Isothiocyanate (FITC). PDA@FITC-MPD was prepared following the aforementioned method. PDA@FITC-MPD was administered orally to mice. In vivo fluorescence intensity was measured to track the retention time and location of PDA@FITC-MPD in the gastrointestinal tract. Finally, 3% Dextran Sulfate Sodium (DSS) was used to establish the UC mice model. After 7 days of treatment with PDA@MPD, therapeutic efficacy was assessed via disease activity index (DAI), colon length, histopathological sections, Western blot, qRT-PCR, and ELISA. Results: MPD can be encapsulated by PDA. Compared to the MPD group, PDA@MPD had longer colonic retention and was superior in improving colon damage and intestinal inflammation in the DSS-induced UC mouse model. These results may be related to PDA@MPD's enhanced regulatory effects on tight junction proteins and inflammatory factors. Conclusion: This study shows that the nanodrug PDA@MPD has colon-retention properties, which enhance the therapeutic effects on DSS-induced UC gut damage and inflammation. Significantly, this research provides novel approaches for the development of traditional Chinese medicine formulations.