Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, Australia.
Eur J Pharm Sci. 2010 Oct 9;41(2):219-25. doi: 10.1016/j.ejps.2010.06.010. Epub 2010 Jun 19.
Catechins found in green tea have received considerable attention due to their favourable biological properties which include cardioprotective, neuroprotective and anti-cancer effects. However, their therapeutic potential is limited by their low oral bioavailability, attributed to poor stability and intestinal absorption. We encapsulated (+)-catechin (C) and (-)-epigallocatechin gallate (EGCg) in chitosan nanoparticles (CS NP) as a means of enhancing their intestinal absorption. Using excised mouse jejunum in Ussing chambers, encapsulation significantly enhanced (p<0.05) intestinal absorption. The cumulative amounts transported after encapsulation were significantly higher (p<0.05), i.e. 302.1+/-46.1 vs 206.8+/-12.6ng/cm(2) and 102.7+/-12.4 vs 57.9+/-7.9ng/cm(2) for C and EGCg, respectively. The mechanism by which absorption was enhanced was not through an effect of CS NPs on intestinal paracellular or passive transcellular transport processes (as shown by transport of (14)C-mannitol and (3)H-propranolol) or an effect on efflux proteins (as shown by transport of (3)H-digoxin) but was likely due to stabilization of catechins after encapsulation (99.7+/-0.7 vs 94.9+/-3.8% and 56.9+/-3.0 vs 1.3+/-1.7% of the initial C and EGCg concentration remaining, respectively). This study demonstrates that encapsulation of catechins in CS NPs enhances their intestinal absorption and is a promising strategy for improving their bioavailability.
儿茶素存在于绿茶中,因其具有心脏保护、神经保护和抗癌作用等有利的生物学特性而受到广泛关注。然而,由于其稳定性差和肠道吸收不良,导致其口服生物利用度低,从而限制了其治疗潜力。我们将(+)-儿茶素(C)和(-)-表没食子儿茶素没食子酸酯(EGCg)包封在壳聚糖纳米粒子(CS NP)中,以提高其肠道吸收。在 Ussing 室中使用离体小鼠空肠,包封显著增强(p<0.05)了肠道吸收。包封后转运的累积量明显更高(p<0.05),即 302.1+/-46.1 和 102.7+/-12.4ng/cm(2) 与 206.8+/-12.6 和 57.9+/-7.9ng/cm(2) 相比,分别为 C 和 EGCg。吸收增强的机制不是通过 CS NPs 对肠道细胞旁或被动跨细胞转运过程的影响(如(14)C-甘露醇和(3)H-心得安的转运所示),也不是对流出蛋白的影响(如(3)H-地高辛的转运所示),而是由于包封后儿茶素的稳定(分别为 99.7+/-0.7 和 56.9+/-3.0% 与 94.9+/-3.8% 和 1.3+/-1.7% 为初始 C 和 EGCg 浓度的剩余)。本研究表明,将儿茶素包封在 CS NP 中可以增强其肠道吸收,是提高其生物利用度的一种有前途的策略。
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