Nanoparticle Processing in the Solid State Dramatically Increases the Cell Membrane Permeation of a Cholesterol-Lowering Drug, Probucol
Nanoparticle Processing in the Solid State Dramatically Increases the Cell Membrane Permeation of a Cholesterol-Lowering Drug, Probucol
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DOI：
10.1021/mp9000487
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发表时间：
2009-05-01
影响因子：
4.9
通讯作者：
Tomono, Kazuo
中科院分区：
文献类型：
--
作者：
Fukami, Toshiro;Ishii, Tatsuya;Tomono, Kazuo
高胆固醇水平（或高胆固醇血症）与许多疾病有关，特别是与冠心病的风险有关。普罗布考通常用于降低血液中的胆固醇。虽然该药物的有效性很大程度上取决于其溶解度，但不幸的是，它几乎不溶（水中溶解度为 5 ng/mL）。因此，有必要开发提高其溶解度和生物利用度并提高药物效率的方法。在这里，我们展示了一种新方法增加了普罗布考在水中的溶解度及其渗透细胞膜的能力。这种将药物加工成纳米颗粒的新方法利用了 PBC 普罗布考与十二烷基硫酸钠和甲基丙烯酸共聚物的研磨。固态核磁共振实验揭示了普罗布考的多晶型状态以及该药物从结晶态到无定形态的转化，并确定了其与共聚物的接近性，因为研磨过程能够形成纳米颗粒。
High cholesterol levels (or hypercholesterolemia) are linked with many diseases, particularly with the risk of coronary heart diseases. Probucol is commonly used to reduce cholesterol in blood. While the effectiveness of this drug highly depends on its solubility, unfortunately, it is nearly insoluble (solubility is 5 ng/mL in water). Therefore, it is essential to develop approaches to increase its solubility and bioavailability and to enhance the efficiency of the drug. Here we show that a new method increases the solubility of probucol in water and its ability to permeate cell membranes. This new method of processing the drug in a nanoparticle utilizes the grinding of PBC probucol together with sodium dodecylsulfate and methacrylic copolymer. Solid-state NMR experiments reveal the polymorphic state of probucol and the conversion of this drug from crystalline to the amorphous state, and determine its nearness to the copolymer due to the grinding process that enables the formation of nanoparticles.