去甲斑蝥素纳米结构脂质载体的释药特性、在体肠吸收及其安全性评价  

Study on in vitro release characteristics,intestinal absorption and safety evaluation of norcantharidin loaded nanostructured lipid carrier

作　　者：伍晓萍 晏子俊 杨坤[3] 位盼盼 邓萌玥 马丙锁 夏谍 丁俞珍 朱玉莲 陈彤 WU Xiao-ping;YAN Zi-jun;YANG Kun;WEI Pan-pan;DENG Meng-yue;MA Bing-suo;XIA Die;DING Yu-zhen;ZHU Yu-lian;CHEN Tong(School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products,Kunming Medical University,Kunming 650500,Yunnan Province,China;Department of Pharmacy,Ziyang People’s Hospital,Ziyang 641300,Sichuan Province,China;Department of Pharmacy,Panzhihua Central Hospital,Panzhihua 617067,Sichuan Province,China)

机构地区：[1]昆明医科大学药学院暨云南省天然药物药理重点实验室,云南昆明650500 [2]资阳市人民医院药学部,四川资阳641300 [3]攀枝花市中心医院药学部,四川攀枝花617067

出　　处：《中国临床药理学杂志》2023年第10期1485-1489,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金地区科学基金资助项目(81760698);第七批云南省高校工程研究中心立项建设项目“云南省高校云南特色植物多糖工程研究中心立项建设”基金资助项目([2019]-57);云南省科学技术厅地方高校联合专项-面上基金资助项目(202001BA070001-041);四川省中医药管理局科研课题基金资助项目(2020JC0086);云南省天然药物药理重点实验室开放基金重点基金资助项目(YKLPNP-K2302)。

摘　　要：目的制备去甲斑蝥素纳米结构脂质载体(NCTD-NLC),考察其物理表征、释药特性和在体肠吸收情况,初步评价其安全性。方法用薄膜分散法制备NCTD-NLC,用透射电镜和激光粒度仪进行物理表征,用葡聚糖凝胶柱法测定包封率,用动态透析法评价释药特性,用单向灌流模型考察大鼠在体肠吸收情况,用溶血性实验评价其安全性。结果NCTD-NLC透射电镜下为圆形或椭圆形,粒径为(90.97±2.65)nm,多分散性指数为0.24±0.02,Zeta电位为(-4.82±1.07)mV,测得包封率为(81.27±0.49)%。体外释放表明,NCTD-NLC释药速度更慢,有一定的缓释作用。在体肠吸收实验表明,NCTD-NLC在4个肠段和胃部的吸收百分率(W)、吸收速率常数(Kα)和有效渗透系数(Peff)均大于游离NCTD,NCTD-NLC在胃、十二指肠、回肠、空肠、结肠的W分别是游离NCTD的2.21、1.99、1.50、2.16和4.73倍,其Kα分别是游离NCTD的2.10、1.80、1.47、2.10和3.99倍,NCTD-NLC在十二指肠、回肠、空肠、结肠的Peff分别是游离NCTD的2.42、1.62、2.62和5.49倍。NCTD和NCTD-NLC几乎不溶血。结论NCTD-NLC有很好的体外释放特性,可增加NCTD的胃肠吸收,可注射给药。Objective To prepare Norcantharidin loaded nanostructured lipid carrier(NCTD-NLC)and study its physical characterization,in vitro release characteristics,intestinal absorption in vivo and safety evaluation.Methods NCTD-NLC was prepared by thin film dispersion method.Physical characterization was identified by transmission electron microscope and laser particle size analyzer.The dialysis was used to evaluate the drug release characteristics.The absorption site and the effect of drug concentration on intestinal absorption of NCTD-NLC in rats were studied by one-way perfusion in vivo.The safety was evaluated by hemolytic test.Results NCTD-NLC was circular or elliptical under transmission electron microscope.The average particle size and the polydispersity index(PDI)for NCTD-NLC were(90.97±2.65)nm and 0.24±0.02.The Zeta potential for NCTD-NLC was(-4.82±1.07)mV.And the value of the encapsulation efficiency for NCTD-NLC was(81.27±0.49)%.The in vitro release results showed that the release rate of NCTD-NLC was slower and had sustained-release effect.The in vivo intestinal absorption experiments showed that the absorption percentage(W),absorption rate constant(Kα)and effective permeability coefficient(Peff)of NCTD-NLC in four intestinal segments and stomach were higher than those of free NCTD.The W of NCTD-NLC in stomach,duodenum,ileum,jejunum,and colon were 2.21,1.99,1.50,2.16 and 4.73 times that of free NCTD.The Kαof NCTD-NLC were 2.10,1.80,1.47,2.10 and 3.99 times that of free NCTD.The Peff of NCTD-NLC in duodenum,ileum,jejunum,and colon were 2.42,1.62,2.62 and 5.49 times that of free NCTD.NCTD and NCTD-NLC did not have obvious vascular hemolysis reaction.Conclusion NCTD-NLC can improve the in vitro release characteristics and enhance the gastrointestinal absorption of NCTD,which can be used for injection.

关 键 词：去甲斑蝥素 纳米结构脂质载体 释药特性 肠吸收 

分 类 号：R979.1[医药卫生—药品]