School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311402, China.
J Nanobiotechnology. 2024 Jun 1;22(1):305. doi: 10.1186/s12951-024-02586-2.
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.
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.
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.
肾纤维化是一种与慢性肾脏病（CKD）相关的进行性过程，导致肾功能受损。传统中药中的活性成分，如大黄素（EMO）和齐墩果酸（AA），具有很强的抗纤维化特性。然而，EMO 和 AA 的口服给药导致生物利用度低，肾脏积累有限。此外，虽然口服益生菌已通过肠道微生物群调节被接受用于 CKD 治疗，但一个重大挑战在于确保它们在给药时的存活能力。因此，我们的研究旨在通过创新的共递药策略来解决肾纤维化和肠道微生物群失衡的问题。
在这项研究中，我们开发了酵母细胞壁颗粒（YCWPs）包裹 EMO 和 AA 自组装纳米颗粒（NPYs），并将其与干酪乳杆菌 Zhang 一起嵌入壳聚糖/海藻酸钠（CS/SA）微凝胶中。所开发的微凝胶对负载的 NPYs 表现出显著的控制释放特性，并延长了干酪乳杆菌 Zhang（L. casei Zhang）在肠道中的保留时间。此外，体内分布表明，微凝胶携带的 NPYs 显著积聚在大鼠梗阻肾脏中，从而大大增加了受损肾脏中 EMO 和 AA 的积累。更重要的是，通过基于酵母细胞壁的搭便车递送和肠道微生物群的正向调节，我们的微凝胶具有这种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。
总之，我们的工作为基于纳米药物和益生菌的搭便车共递药提供了一种新的策略，以实现疾病治疗和靶向肠道菌群调节的协同效应，从而为肾纤维化的治疗提供了一种新的策略。
