脂蟾毒配基PLGA-TPGS纳米粒在小鼠体内肝的靶向性
发布时间：2018-07-14 11:28
【摘要】：目的:研究脂蟾毒配基(Resibufogenin,RBG)/香豆素-6(Coumarin-6,C6)乙交酯丙交酯共聚物-维生素E聚乙二醇1000琥珀酸酯(PLGA-TPGS)纳米粒(RBG/C6-loaded PLGA-TPGS nanoparticles,RCPTN)在小鼠体内的分布及对小鼠肝脏的靶向性。方法:建立RP-HPLC法测定RBG在小鼠血浆及肝、心、脾、肺和肾等生物样品中的浓度,将RCPTN和RBG溶液(RS)经小鼠尾静脉注射后,测定不同给药时间后小鼠血浆及各脏器中的RBG浓度。采用靶向指数(TI)、选择性指数(SI)、相对靶向效率(Re)和靶向效率(Te)4个指标,同时通过对各器官进行冰冻切片,荧光倒置显微镜下观察荧光纳米粒RCPTN在各器官的分布,定性、定量的全面评价RCPTN对肝脏的靶向性。结果:除SI血浆在0.08,0.5 h时,TI和SI的数值均大于1,表明RCPTN在各时间点对肝脏的靶向作用良好;在血浆、肝、心、脾、肺、肾中的Re分别为2.1、40.1、1.1、16.4、11.7、1.4,即在整个考察时间范围内,RCPTN在肝脏中的药时曲线下面积(AUC)是RS的40.1倍,表明载药纳米粒能将药物更好的传递至肝脏;RCPTN在血浆、心、脾、肺、肾中的Te均大于3,表明RBG在肝脏比血浆和其他脏器匀浆中的AUC高达3倍以上,且在心脏中的Te(28.1)是RS在心脏中Te(0.8)的35.1倍,表明RCPTN具有良好的肝脏靶向作用,且可显著降低RBG在心脏中的分布。冰冻切片图可见在1 h的RCPTN组小鼠各器官中,肝中荧光分布面积最大,其次是脾和肺,最后是肾和心。表明RCPTN静脉注射后对肝脏有良好的靶向性,这与用TI、SI、Re和Te 4个靶向指标评价RCPTN对肝脏的靶向性结果是一致的。结论:RCPTN对小鼠肝脏有良好的靶向作用,在心脏分布较少。
[Abstract]:Objective: to study the distribution of resifogenin (RBG) / coumarin-6 (Coumarin-6) glycolide copolymer (PLGA-TPGS) nanoparticles in mice and its targeting to mouse liver. Methods: a RP-HPLC method was established for the determination of RBG concentrations in plasma, liver, heart, spleen, lung and kidney of mice. RCPTN and RBG solution (RS) were injected into tail vein of mice. The target index (TI), selectivity index (SI), relative targeting efficiency (re) and targeting efficiency (Te) were used. At the same time, the distribution of fluorescent nanoparticles RCPTN in each organ was observed by fluorescence inversion microscope. The liver targeting of RCPTN was evaluated quantitatively and comprehensively. Results: the values of TI and SI in plasma were higher than 1 at 0. 08 h, indicating that RCPTN had a good targeting effect on liver at different time points, and on plasma, liver, heart, spleen and lung. Re in the kidney was 2.1g / 40.1g / L 1.1g / 16.4 / 11.71.4. that is, the area under the curve (AUC) of RCPTN in the liver was 40.1 times higher than that of RS in the whole investigation time range, which indicated that the drug loaded nanoparticles could better transfer the drug to liver RCPTN in plasma, heart, spleen and lung. Te in kidney is more than 3, indicating that RBG has more than 3 times AUC in liver than in plasma and other organ homogenate, and Te (28.1) in heart is 35.1 times higher than that in RS in heart, which indicates that RCPTN has good liver targeting effect. The distribution of RBG in the heart was significantly decreased. Frozen sections showed that in the RCPTN group for 1 h, the fluorescence distribution in the liver was the largest, followed by the spleen and lung, and finally the kidney and heart. The results showed that RCPTN had good targeting to liver after intravenous injection, which was consistent with the evaluation of liver targeting by TIP-SIRe and Te. ConclusionTwo-RCPTN has a good targeting effect on the liver of mice and is less distributed in the heart.
【作者单位】： 大连医科大学基础医学院;大连医科大学药学院;大连医科大学;
【基金】：辽宁省自然科学基金项目(编号:2015020308)
【分类号】：R943;R965
，
本文编号：2121504
[Abstract]:Objective: to study the distribution of resifogenin (RBG) / coumarin-6 (Coumarin-6) glycolide copolymer (PLGA-TPGS) nanoparticles in mice and its targeting to mouse liver. Methods: a RP-HPLC method was established for the determination of RBG concentrations in plasma, liver, heart, spleen, lung and kidney of mice. RCPTN and RBG solution (RS) were injected into tail vein of mice. The target index (TI), selectivity index (SI), relative targeting efficiency (re) and targeting efficiency (Te) were used. At the same time, the distribution of fluorescent nanoparticles RCPTN in each organ was observed by fluorescence inversion microscope. The liver targeting of RCPTN was evaluated quantitatively and comprehensively. Results: the values of TI and SI in plasma were higher than 1 at 0. 08 h, indicating that RCPTN had a good targeting effect on liver at different time points, and on plasma, liver, heart, spleen and lung. Re in the kidney was 2.1g / 40.1g / L 1.1g / 16.4 / 11.71.4. that is, the area under the curve (AUC) of RCPTN in the liver was 40.1 times higher than that of RS in the whole investigation time range, which indicated that the drug loaded nanoparticles could better transfer the drug to liver RCPTN in plasma, heart, spleen and lung. Te in kidney is more than 3, indicating that RBG has more than 3 times AUC in liver than in plasma and other organ homogenate, and Te (28.1) in heart is 35.1 times higher than that in RS in heart, which indicates that RCPTN has good liver targeting effect. The distribution of RBG in the heart was significantly decreased. Frozen sections showed that in the RCPTN group for 1 h, the fluorescence distribution in the liver was the largest, followed by the spleen and lung, and finally the kidney and heart. The results showed that RCPTN had good targeting to liver after intravenous injection, which was consistent with the evaluation of liver targeting by TIP-SIRe and Te. ConclusionTwo-RCPTN has a good targeting effect on the liver of mice and is less distributed in the heart.
【作者单位】： 大连医科大学基础医学院;大连医科大学药学院;大连医科大学;
【基金】：辽宁省自然科学基金项目(编号:2015020308)
【分类号】：R943;R965
，
本文编号：2121504
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