Chitosan nanoparticles enhance the plasma exposure of (-)-epigallocatechin gallate in mice through an enhancement in intestinal stability
Chitosan nanoparticles enhance the plasma exposure of (-)-epigallocatechin gallate in mice through an enhancement in intestinal stability
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DOI：
10.1016/j.ejps.2011.09.004
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发表时间：
2011-10-09
影响因子：
4.6
通讯作者：
Larson, Ian
中科院分区：
文献类型：
--
作者：
Dube, Admire;Nicolazzo, Joseph A.;Larson, Ian
绿色茶儿茶素（-）-表没食子儿茶素没食子酸酯（epigallocatechin gallate，EGCG）具有抗氧化、神经保护和抗癌等多种药理作用，近年来引起了人们的广泛关注。然而，口服食用后EGCG的治疗潜力受到其吸收不良的限制。为了解决这个问题，将EGCG封装在壳聚糖-三聚磷酸盐纳米颗粒（CS NPs）中，并在瑞士远交小鼠中评估了EGCG的口服吸收。相对于EGCG溶液，CS NP的施用将总EGCG的血浆暴露增强了1.5倍，血浆AUC（（0 - 5 h））值为116.4 +/- 4.1和179.3 +/- 10.8 nM.h（平均值+/- s.d.，n = 3 - 5）。与EGCG的血浆暴露增加相关的是CS NP给药后小鼠胃和空肠中EGCG浓度的增加。在CS NP包封后，观察到EGCG对空肠的表观暴露（AUC（j））增加2.3倍，AUC（j（0 - 5 h））值为5.3 +/- 1.1和12.3 +/- 1.5 μ M. h（平均值+/- s.d.，n = 3 - 5）。增强暴露的表没食子儿茶素没食子酸酯的空肠可能是负责增加血浆中的表没食子儿茶素没食子酸酯浓度。这项研究的结果表明，CS纳米颗粒可能是一种有用的方法，用于增强口服递送，和治疗应用，表没食子儿茶素没食子酸酯在许多疾病条件。(C)出版社：Elsevier B. V.
The green tea catechin (-)-epigallocatechin gallate (EGCG) has attracted significant research interest due to its beneficial therapeutic effects, which include anti-oxidant, neuro-protective and anti-cancer effects. However, the therapeutic potential of EGCG following oral consumption is limited by its poor absorption. To address this issue, EGCG has been encapsulated in chitosan-tripolyphosphate nanoparticles (CS NPs) and the oral absorption of EGCG evaluated in Swiss Outbred mice. Administration of the CS NPs enhanced the plasma exposure of total EGCG by a factor of 1.5 relative to an EGCG solution, with plasma AUC((0 - 5 h)) values of 116.4 +/- 4.1 and 179.3 +/- 10.8 nM.h (mean +/- s.d., n = 3 - 5) for the EGCG solution and CS NPs, respectively. Associated with the increased plasma exposure of EGCG was an enhancement in concentrations of EGCG in the stomach and jejunum of mice following CS NP administration. A 2.3-fold increase in the apparent exposure of EGCG to the jejunum (AUC(j)) was observed following CS NP encapsulation, with AUC(j(0 - 5 h)) values of 5.3 +/- 1.1 and 12.3 +/- 1.5 mu M.h (mean +/- s.d., n = 3 - 5) for the EGCG solution and CS NPs, respectively. The enhanced exposure of EGCG to the jejunum was likely responsible for the increased plasma concentrations of EGCG. The findings from this study suggest that CS NPs may be a useful approach for enhancing oral delivery, and therapeutic application, of EGCG in a number of disease conditions. (C) 2011 Published by Elsevier B.V.