背景:肾纤维化是与慢性肾脏病(CKD)相关的进行性过程,导致肾功能受损。传统中草药中的有效成分,如大黄素(EMO)和积雪草酸(AA),表现出有效的抗纤维化特性。然而,EMO和AA的口服给药导致低生物利用度和有限的肾脏蓄积。此外,虽然口服益生菌已被接受通过肠道微生物群调节治疗CKD,一个重大挑战在于确保它们在管理时的生存能力。因此,我们的研究旨在通过创新的共同给药策略解决肾脏纤维化和肠道微生物群失衡.
结果:在这项研究中,我们开发了封装EMO和AA自组装纳米颗粒(NPYs)的酵母细胞壁颗粒(YCWPs),还有干酪乳杆菌张,在壳聚糖/海藻酸钠(CS/SA)微凝胶中。开发的微凝胶对负载的NPYs显示出显着的控释特性,并延长了干酪乳杆菌的保留时间(L。CaseiZhang)在肠道中。此外,体内生物分布表明,微凝胶携带的NPYs在大鼠阻塞的肾脏中显著积累,从而显著增加受损肾脏中EMO和AA的积累。更重要的是,通过基于酵母细胞壁的搭便车运输和肠道微生物群的正向调节,我们的微凝胶与治疗和调节相互作用的协同策略可以调节TGF-β/Smad信号通路,从而有效改善单侧输尿管梗阻(UUO)大鼠的肾纤维化.
结论:结论:我们的工作为肾脏纤维化的治疗提供了一种基于纳米药物和益生菌的搭便车共同递送的新策略,以实现疾病治疗和靶向肠道菌群调节的协同作用.
BACKGROUND: Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies.
RESULTS: In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA)
microgels. The developed
microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our
microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-β/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats.
CONCLUSIONS: In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation.