Kang Dong,1,* Xin Wang,1– 3,* Ze-jia Zhou,1– 3 Xin-ru Zheng,1– 3 Zhuang-peng Chang,1 Rui Zhao,1,2 Jun-jin Liu,1– 3 Rui-gang Hou,1– 3 Xiao Zhang,1– 3 Yun-yun Shao1– 3 

1Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yun-yun Shao; Rui-gang Hou, Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China, Tel +86 351-3365405, Email shaoyunyun4466@163.com; ruiganghou9966@163.com

Introduction: Ulcerative colitis (UC) is a chronic intestinal disease characterized by spleen-lung qi deficiency and dampness-pathogenic obstruction. Although there are various treatment options available, patients frequently encounter significant drug-related side effects. Previous studies have shown the potential of Codonopsis Radix polysaccharides A (CPA) in treating UC, but their limited bioavailability has restricted their clinical use. Therefore, the objective of this study was to develop a novel formulation that can address the aforementioned limitations and assess its potential advantages.
Methods and Results: We synthesized a negatively charged amphipathic prodrug called CPA-SA-DHA (CSD), which consists of CPA as the hydrophilic component, and succinic anhydride and docosahexaenoic acid as the hydrophobic segments. The CSD nanoparticles obtained had a particle size of 180.0 ± 3.2 nm, a negative zeta potential of − 29.8 ± 5.3 mV, and a uniform shape with a PDI index of 0.230 ± 0.003. The interaction between positive and negative charges significantly increased the retention time of CSD nanoparticles in the colonic microenvironment. Furthermore, CSD nanoparticles demonstrated enhanced bioavailability in UC mice compared to CPA. Additionally, we observed that CSD nanoparticles exhibited therapeutic effects on DSS-induced UC mice by regulating the diversity and abundance of gut microbiota. This effect may be mediated by the inhibition of pro-inflammatory signaling pathways TLR4/NF-κB.
Conclusion: These findings confirm the potential of CSD nanoparticles as a promising treatment option for UC.

Keywords: ulcerative colitis, Codonopsis Radix polysaccharide, succinic acid, docosahexaenoic acid, nanoparticles