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载药介孔硅纳米结构用于香豆素衍生物的控制释放:一种新型的热疗效果测试。

Nanostructure-loaded mesoporous silica for controlled release of coumarin derivatives: a novel testing of the hyperthermia effect.

机构信息

Chemistry Department, Tanta University, Tanta, Egypt.

出版信息

Eur J Pharm Biopharm. 2011 Jan;77(1):66-74. doi: 10.1016/j.ejpb.2010.10.007. Epub 2010 Oct 23.

Abstract

The synthesis of three types of mesoporous materials is reported: pure mesoporous silica (MCM-41), a nanocomposite of mesoporous silica with hydroxyapatite (MCM-41-HA) and mesoporous silica/gold nanorods nanocomposite (MCM-41-GNRs). The mesoporous materials were characterized by X-ray diffraction, N(2) adsorption isotherms, FTIR spectroscopy, transmission electron microscopy, and scanning electron microscopy. The samples were loaded with coumarin thiourea derivatives (I-IV) having functional groups of varying sizes and the in vitro release assays were monitored, and the release behavior was investigated as a function of soaking time in simulated body fluid. Two release stages were obtained in MCM-41, MCM-41-HA and MCM-41-GNRs loaded samples with the early release stages accounting for about 30% of loaded derivatives. These early release stages are characterized by Higuchi rate constant values nearly twice the values associated with the second release stages. The influence of substituent size on the release rate constants was explained in terms of sorption sites and hydrogen bonding with silanol groups on silicates. The release of coumarin derivatives loaded on MCM-41, MCM-41-HA and MCM-41-GNRs occurs over remarkably long time of the order of about 260 h with faster release rates in loaded MCM-41 and MCM-41-GNRs samples compared with MCM-41-HA ones. The role of hyperthermia effect in enhancing release rates was investigated by subjecting loaded MCM-41-GNRs to near infrared (NIR) radiation at 800 nm. This would be of significance in targeted drug release using hyperthermia effect. Unlike hydroxyl apatite, loading MCM-41 with gold nanorods does not affect the release kinetics. Only when these samples are irradiated with NIR photons, does the release occur with enhanced rates. This property could be valuable in selected targeting of drugs.

摘要

报道了三种类型的介孔材料的合成

纯介孔硅(MCM-41)、介孔硅与羟基磷灰石的纳米复合物(MCM-41-HA)和介孔硅/金纳米棒纳米复合物(MCM-41-GNRs)。通过 X 射线衍射、N2 吸附等温线、FTIR 光谱、透射电子显微镜和扫描电子显微镜对介孔材料进行了表征。将香豆素硫脲衍生物(I-IV)负载到样品中,这些衍生物具有不同大小的官能团,并监测了体外释放实验,研究了释放行为与在模拟体液中浸泡时间的关系。在负载有 MCM-41、MCM-41-HA 和 MCM-41-GNRs 的样品中,得到了两个释放阶段,其中早期释放阶段占负载衍生物的约 30%。这些早期释放阶段的 Higuchi 速率常数值几乎是第二释放阶段的两倍。取代基大小对释放速率常数的影响可以用硅酸盐上的吸附位和与硅醇基的氢键来解释。MCM-41、MCM-41-HA 和 MCM-41-GNRs 负载的香豆素衍生物的释放时间非常长,约为 260 h,负载的 MCM-41 和 MCM-41-GNRs 样品的释放速率比 MCM-41-HA 样品快。通过将负载的 MCM-41-GNRs 置于 800nm 的近红外(NIR)辐射下,研究了热效应增强释放速率的作用。这对于利用热效应进行靶向药物释放具有重要意义。与羟基磷灰石不同,负载金纳米棒不会影响释放动力学。只有当这些样品受到近红外光子的照射时,才会以增强的速率释放。这种特性在药物的选择性靶向中可能具有价值。

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