Thiolated chitosan/alginate/Emodin nanoparticles alleviate chronic kidney disease via gut microbiota regulation and intestinal barrier protection

Chronic kidney disease (CKD) is closely associated with gut microbiota dysbiosis and impaired intestinal barrier function, yet effective therapeutic strategies targeting the gut-kidney axis remain limited. This study aimed to develop a thiolated chitosan/sodium alginate-based nanoparticle system encapsulating emodin (TCS/ALG/Emodin-NPs), and to evaluate its therapeutic efficacy in CKD through modulation of gut microbiota and intestinal barrier protection. The nanoparticles were synthesized, characterized, and orally administered to CKD mice at varying doses, with irbesartan as a positive control. Our results showed that TCS/ALG/Emodin-NPs significantly improved renal function, reduced renal fibrosis, and restored gut microbiota balance, particularly increasing beneficial bacteria such as <i>Lactobacillus</i>. They also enhanced intestinal tight junction integrity and suppressed systemic inflammation. In a hydrogen peroxide-induced Caco-2 cell model, Emodin-NPs more effectively attenuated oxidative stress and apoptosis compared to free Emodin. The findings suggest that TCS/ALG/Emodin-NPs are a promising strategy for CKD treatment by reshaping gut microbiota and enhancing intestinal function.IMPORTANCEWhile the gut-kidney axis has emerged as a critical target in chronic kidney disease (CKD) management, therapeutic strategies leveraging this pathway remain limited. This study demonstrates that colon-targeted TCS/ALG/Emodin-NPs not only enhance drug bioavailability but also exert dual therapeutic effects by rectifying gut dysbiosis and reinforcing intestinal barrier function-key mechanisms implicated in CKD progression. The superior efficacy of TCS/ALG/Emodin-NPs over free Emodin underscores the transformative potential of nanoparticle delivery systems in overcoming the pharmacokinetic limitations of herbal medicines. This research opens new avenues for the development of microbiota-targeted, anti-inflammatory therapies that can complement existing CKD treatments and potentially slow disease progression in affected patients.