Department of Endocrinology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, People's Republic of China.
State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, People's Republic of China.
Int J Nanomedicine. 2024 Nov 19;19:12099-12110. doi: 10.2147/IJN.S487519. eCollection 2024.
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterised by insulin resistance, hyperglycaemia, and inflammation, with oxidative stress contributing to its progression. Curcumin (CUR), known for its anti-inflammatory, antioxidant, and insulin sensitising effects, has shown potential for the treatment of T2DM but is limited by low solubility and bioavailability. This study investigated long-circulating curcumin-loaded liposomes (CUR-LPs) to improve curcumin stability, solubility, and circulation and assessed their effect on insulin resistance in a murine model of T2DM.
CUR-LPs were prepared using the ethanol injection method and characterized for morphology, particle size, zeta potential, encapsulation efficiency, drug-loading capacity, and in vitro release. Cell viability was tested on murine L929 cells. In a T2DM murine model, after four weeks of CUR-LP treatment, inflammatory markers TNF-α and IL-6 were measured by real-time polymerase chain reaction, and liver tissues were analyzed for glutathione (GSH) and superoxide dismutase (SOD) via colorimetry.
CUR-LPs were spherical, with an average diameter of (249 ± 2.3) nm and a zeta potential of (-33.5 ± 0.8) mV. They exhibited an encapsulation efficiency of (99.2 ± 0.5) %and a drug-loading capacity of (1.63 ± 0.02) %. CUR embedding in liposomes significantly maintained CUR release. In L929 cells, over 80% viability was maintained at 12 uM CUR concentration after 24 h. In HFD/STZ-induced T2DM mice, CUR-LPs improved blood glucose and insulin levels more efficiently than free CUR, and CUR-LPs also reduced hepatic inflammation (TNF-α, IL-6), enhanced hepatic GSH and SOD, and attenuated liver injury.
CUR-LPs improved glucose metabolism and insulin resistance in HFD/STZ-induced T2DM mice, which may be associated with a decrease in liver inflammation and oxidative stress.
2 型糖尿病（T2DM）是一种代谢紊乱疾病，其特征为胰岛素抵抗、高血糖和炎症，而氧化应激则促进其进展。姜黄素（CUR）具有抗炎、抗氧化和胰岛素增敏作用，已显示出治疗 T2DM 的潜力，但由于溶解度和生物利用度低而受到限制。本研究旨在通过制备长循环姜黄素载脂蛋白（CUR-LPs）来提高 CUR 的稳定性、溶解度和循环，并评估其对 T2DM 小鼠模型胰岛素抵抗的影响。
采用乙醇注入法制备 CUR-LPs，并对其形态、粒径、zeta 电位、包封率、载药量和体外释放进行表征。在小鼠 L929 细胞上测试细胞活力。在 T2DM 小鼠模型中，经 4 周 CUR-LP 治疗后，通过实时聚合酶链反应测定炎症标志物 TNF-α和 IL-6，通过比色法测定肝组织谷胱甘肽（GSH）和超氧化物歧化酶（SOD）。
CUR-LPs 呈球形，平均粒径为（249±2.3）nm，zeta 电位为（-33.5±0.8）mV。包封率为（99.2±0.5）%，载药量为（1.63±0.02）%。姜黄素包埋在脂质体中可显著维持 CUR 的释放。在 L929 细胞中，在 24 小时时，浓度为 12 μM 的 CUR 可保持超过 80%的细胞活力。在 HFD/STZ 诱导的 T2DM 小鼠中，与游离 CUR 相比，CUR-LPs 更有效地改善血糖和胰岛素水平，并且 CUR-LPs 还降低了肝炎症（TNF-α，IL-6），增强了肝 GSH 和 SOD，并减轻了肝损伤。
CUR-LPs 改善了 HFD/STZ 诱导的 T2DM 小鼠的葡萄糖代谢和胰岛素抵抗，这可能与肝脏炎症和氧化应激的减少有关。
