Abstract：
Liver injury caused by type-II diabetes mellitus (DM) is a significant public-health concern worldwide. We used chitosan (CS) to modify dihydromyricetin (DHM)-loaded liposomes (DL) through charge interaction. The effect of CS-modified DL (CDL) on liver injury in mice suffering from DM was investigated in vivo and in vitro. CDL exhibited superior antioxidant capacity and stability. Pharmacokinetic analyses revealed a 3.23- and 1.92-fold increase in the drug concentration-time curve (953.60 ± 122.55 ng/mL/h) in the CDL-treated group as opposed to the DHM-treated group (295.15 ± 25.53 ng/mL/h) and DL-treated group (495.31 ± 65.21 ng/mL/h). The maximum drug concentration in blood (Tmax) of the CDL group saw a 2.26- and 1.21-fold increase compared with that in DHM and DL groups. We observed a 1.49- and 1.31-fold increase in the maximum drug concentration in blood (Cmax) in the CDL group compared with that in DHM and DL groups. Western blotting suggested that CDL could alleviate liver injury in mice suffering from DM by modulating inflammatory factors and the transforming growth factor-β1/Smad2/Smad3 signaling pathway. In conclusion, modification of liposomes using CS is a viable approach to address the limitations of conventional liposomes and insoluble drugs.
摘要：
由II型糖尿病（DM）引起的肝损伤是全球重大公共卫生问题。我们使用壳聚糖（CS）通过电荷相互作用修饰负载二氢杨梅素（DHM）的脂质体（DL）。在体内和体外研究了CS修饰的DL（CDL）对DM小鼠肝损伤的影响。CDL表现出优异的抗氧化能力和稳定性。药代动力学分析显示，与DHM治疗组（295.15±25.53ng/mL/h）和DL治疗组（495.31±65.21ng/mL/h）相比，CDL治疗组的药物浓度-时间曲线（953.60±122.55ng/mL/h）增加了3.23倍和1.92倍。与DHM和DL组相比，CDL组的血液中最大药物浓度（Tmax）增加了2.26倍和1.21倍。我们观察到，与DHM和DL组相比，CDL组的血液中最大药物浓度（Cmax）分别增加了1.49和1.31倍。Westernblot提示CDL可通过调节炎症因子和转化生长因子-β1/Smad2/Smad3信号通路减轻DM小鼠肝损伤。总之,使用CS修饰脂质体是解决常规脂质体和不溶性药物局限性的可行方法。
