Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles
Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles
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DOI：
10.1016/j.jconrel.2008.10.002
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发表时间：
2009-02-10
影响因子：
10.8
通讯作者：
Lou, HongXiang
中科院分区：
文献类型：
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作者：
Li, HouLi;Zhao, XiaoBin;Lou, HongXiang
本研究的目的是设计和表征槲皮素固体脂质纳米粒(QT-SLNS)，阐明QT-SLNS的吸收机制，并评价其作为难溶药物口服载体的可能性。采用乳化低温固化法制备了QT-SLN。在透射电子显微镜下，QT-SLN呈球形，平均直径为155.3 nm。平均包封率为91.1%，载药量为13.2%，Zeta电位为-32.2 mV。药物释放符合双相动力学模型，其动力学方程为：100-Q=98.87e(-0.1042t)+42.45e(-0.0258t)。采用大鼠在体灌注法研究了QT-SLN在大鼠胃肠道的吸收情况。结果表明，阿昔洛韦在胃中的吸收百分率仅为6.20%，肠吸收过程为被动扩散的第一过程，主要吸收段为回肠和结肠。大鼠口服QT-SLNS或混悬液50 mg/kg后，进行了药代动力学研究。血药浓度-时间曲线均符合一室模型。QT-SLN对槲皮素混悬液的相对生物利用度为571.4%。血浆中槲皮素的T-max和MRT均延迟。我们的研究提供了证据，证明SLN是一种有价值的口服给药载体，可以促进难于溶于水的药物Qercetin的吸收。(C)2008爱思唯尔B.V.保留所有权利。
The aim of the present study is to design and characterize quercetin-loaded solid lipid nanoparticles (QT-SLNs), clarify the absorption mechanism of QT-SLNs and to evaluate the potential of using solid lipid nanoparticles (SLNs) as an oral delivery carrier for poorly water soluble drugs. QT-SLNs were prepared by an emulsification and low-temperature solidification method. The QT-SLNs presented as spherically shaped under transmission electron microscopy, with an average diameter of 155.3 nm. The average drug entrapment efficiency, drug loading and zeta potential were 91.1%,13.2% and -32.2 mV, respectively. Drug release from QT-SLNs was fitted to a double phase kinetics model and the equation was as follows: 100 - Q = 98.87e(-0.1042t)+42.45e(-0.0258t). The absorption of QT-SLNs in the gastrointestinal (GI) tract was studied using an in situ perfusion method in rats. It was found that the absorption percent in the stomach for 2 h was only 6.20%, the absorption process of intestine was first-process with passive diffusion mechanism, and the main absorptive segments were ileum and colon. A pharmacokinetic study was conducted in rats after oral administration of quercetin at 50 mg/kg in the form of either QT-SLNs or suspension. The plasma concentration-time curves were both fitted to a one-compartment model. The relative bioavailability of QT-SLNs to quercetin suspension was 571.4%. The T-max and MRT for quercetin in plasma were both delayed. Our studies provide evidence that SLNs are valuable as an oral delivery carrier to enhance the absorption of a poorly water soluble drug, quercetin. (C) 2008 Elsevier B.V. All rights reserved.