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脂蟾毒配基PLGA-TPGS納米粒在小鼠體內(nèi)肝的靶向性

發(fā)布時(shí)間: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-維生素E聚乙二醇1000琥珀酸酯(PLGA-TPGS)納米粒(RBG/C6-loaded PLGA-TPGS nanoparticles,RCPTN)在小鼠體內(nèi)的分布及對(duì)小鼠肝臟的靶向性。方法:建立RP-HPLC法測(cè)定RBG在小鼠血漿及肝、心、脾、肺和腎等生物樣品中的濃度,將RCPTN和RBG溶液(RS)經(jīng)小鼠尾靜脈注射后,測(cè)定不同給藥時(shí)間后小鼠血漿及各臟器中的RBG濃度。采用靶向指數(shù)(TI)、選擇性指數(shù)(SI)、相對(duì)靶向效率(Re)和靶向效率(Te)4個(gè)指標(biāo),同時(shí)通過對(duì)各器官進(jìn)行冰凍切片,熒光倒置顯微鏡下觀察熒光納米粒RCPTN在各器官的分布,定性、定量的全面評(píng)價(jià)RCPTN對(duì)肝臟的靶向性。結(jié)果:除SI血漿在0.08,0.5 h時(shí),TI和SI的數(shù)值均大于1,表明RCPTN在各時(shí)間點(diǎn)對(duì)肝臟的靶向作用良好;在血漿、肝、心、脾、肺、腎中的Re分別為2.1、40.1、1.1、16.4、11.7、1.4,即在整個(gè)考察時(shí)間范圍內(nèi),RCPTN在肝臟中的藥時(shí)曲線下面積(AUC)是RS的40.1倍,表明載藥納米粒能將藥物更好的傳遞至肝臟;RCPTN在血漿、心、脾、肺、腎中的Te均大于3,表明RBG在肝臟比血漿和其他臟器勻漿中的AUC高達(dá)3倍以上,且在心臟中的Te(28.1)是RS在心臟中Te(0.8)的35.1倍,表明RCPTN具有良好的肝臟靶向作用,且可顯著降低RBG在心臟中的分布。冰凍切片圖可見在1 h的RCPTN組小鼠各器官中,肝中熒光分布面積最大,其次是脾和肺,最后是腎和心。表明RCPTN靜脈注射后對(duì)肝臟有良好的靶向性,這與用TI、SI、Re和Te 4個(gè)靶向指標(biāo)評(píng)價(jià)RCPTN對(duì)肝臟的靶向性結(jié)果是一致的。結(jié)論:RCPTN對(duì)小鼠肝臟有良好的靶向作用,在心臟分布較少。
[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.
【作者單位】: 大連醫(yī)科大學(xué)基礎(chǔ)醫(yī)學(xué)院;大連醫(yī)科大學(xué)藥學(xué)院;大連醫(yī)科大學(xué);
【基金】:遼寧省自然科學(xué)基金項(xiàng)目(編號(hào):2015020308)
【分類號(hào)】:R943;R965
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本文編號(hào):2121504

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