Wei Guangfei, Song Xu, Fu Yao, Gong Tao, Zhang Quan
Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
School of Pharmacy, Chengdu Medical College, No. 783, Xindu Avenue, Chengdu, Sichuan, 610500, China.
Int J Pharm. 2017 Sep 15;530(1-2):230-238. doi: 10.1016/j.ijpharm.2017.07.072. Epub 2017 Jul 25.
As a mitochondrial uncoupler, 2,4-dinitrophenol (DNP) is proven therapeutically effective against nonalcoholic fatty liver disease (NAFLD) by uncoupling oxidation and phosphorylation. However, a major factor that impedes the clinical application of DNP is the significant side effects derived from its frequent hyperthermia and even death. In this study, we developed an injectable liquid crystal gel (DNP-LC-gel) to reduce the toxicity of DNP. DNP-LC-gel achieved sustained release and maintained DNP plasma concentration at an effective drug level. In a rat model of NAFLD, DNP-LC-gel treated rats reduced hepatic steatosis, liver triglyceride content, plasma triacylglycerol (TG) and total cholesterol (TC) content. Compared with DNP solution (DNP-soln), rats after DNP-LC-gel treatment showed no body temperature toxicity and local irritation. All results above indicated that DNP-LC-gel has a great potential for NAFLD therapy.
作为一种线粒体解偶联剂，2,4-二硝基苯酚（DNP）已被证明通过使氧化与磷酸化解偶联，对非酒精性脂肪性肝病（NAFLD）具有治疗效果。然而，阻碍DNP临床应用的一个主要因素是其频繁导致体温过高甚至死亡所产生的显著副作用。在本研究中，我们开发了一种可注射液晶凝胶（DNP-LC-凝胶）以降低DNP的毒性。DNP-LC-凝胶实现了持续释放，并将DNP血浆浓度维持在有效药物水平。在NAFLD大鼠模型中，接受DNP-LC-凝胶治疗的大鼠肝脏脂肪变性减轻，肝脏甘油三酯含量、血浆三酰甘油（TG）和总胆固醇（TC）含量降低。与DNP溶液（DNP-溶液）相比，接受DNP-LC-凝胶治疗后的大鼠未表现出体温毒性和局部刺激。上述所有结果表明，DNP-LC-凝胶在NAFLD治疗方面具有巨大潜力。
