Department of Pharmacy, Guangxi Medical University, Nanning, People's Republic of China.
The Second Nanning People's Hospital, Nanning, People's Republic of China.
Int J Nanomedicine. 2024 Mar 8;19:2409-2428. doi: 10.2147/IJN.S452194. eCollection 2024.
Nitidine chloride (NC) is a botanical drug renowned for its potent anti-inflammatory, antimalarial, and hepatocellular carcinoma-inhibiting properties; however, its limited solubility poses challenges to its development and application. To address this issue, we have devised a colon-targeted delivery system (NC-CS/PT-NPs) aimed at modulating the dysbiosis of the gut microbiota by augmenting the interaction between NC and the intestinal microbiota, thereby exerting an effect against nonalcoholic fatty liver disease.
The NC-CS/PT-NPs were synthesized using the ion gel method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behavior of the NC-CS/PT-NPs were characterized. Furthermore, the impact of NC-CS/PT-NPs on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice was investigated through serum biochemical analysis, ELISA, and histochemical staining. Additionally, the influence of NC-CS/PT-NPs on intestinal microbiota was analyzed using 16S rDNA gene sequencing.
The nanoparticles prepared in this study have an average particle size of (255.9±5.10) nm, with an encapsulation rate of (72.83±2.13) % and a drug loading of (4.65±0.44) %. In vitro release experiments demonstrated that the cumulative release rate in the stomach and small intestine was lower than 22.0%, while it reached 66.75% in the colon. In vivo experiments conducted on HFD-induced NAFLD mice showed that treatment with NC-CS/PT-NPs inhibited weight gain, decreased serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and lipid levels, improved liver and intestinal inflammation, and altered the diversity of gut microbiota in mice.
This study provides new evidence for the treatment of NAFLD through the regulation of gut microbiota using active ingredients from traditional Chinese medicine.
盐酸小檗碱（NC）是一种具有强大抗炎、抗疟和抑制肝癌作用的植物药，但由于其溶解度有限，限制了其开发和应用。为了解决这个问题，我们设计了一种结肠靶向递药系统（NC-CS/PT-NPs），旨在通过增强 NC 与肠道微生物群的相互作用来调节肠道微生物群的失调，从而对非酒精性脂肪性肝病（NAFLD）发挥作用。
采用离子凝胶法合成 NC-CS/PT-NPs。然后，对 NC-CS/PT-NPs 的粒径分布、形态、载药效率和释放行为进行了表征。此外，通过血清生化分析、ELISA 和组织化学染色研究了 NC-CS/PT-NPs 对高脂肪饮食（HFD）诱导的小鼠非酒精性脂肪性肝病（NAFLD）的影响。此外，还通过 16S rDNA 基因测序分析了 NC-CS/PT-NPs 对肠道微生物群的影响。
本研究制备的纳米粒平均粒径为（255.9±5.10）nm，包封率为（72.83±2.13）%，载药量为（4.65±0.44）%。体外释放实验表明，在胃和小肠中的累积释放率低于 22.0%，而在结肠中达到 66.75%。在 HFD 诱导的 NAFLD 小鼠体内实验中，NC-CS/PT-NPs 治疗抑制了体重增加，降低了血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和脂质水平，改善了肝和肠道炎症，并改变了小鼠肠道微生物群的多样性。
本研究为通过调节肠道微生物群来治疗 NAFLD 提供了新的证据，这是利用中药有效成分治疗疾病的一种新方法。
