Fukami Toshiro, Ishii Tatsuya, Io Takeshi, Suzuki Naoto, Suzuki Toyofumi, Yamamoto Kazutoshi, Xu Jiadi, Ramamoorthy Ayyalusamy, Tomono Kazuo
College of Pharmacy, Nihon University, Chiba 274-8555, Japan.
Mol Pharm. 2009 May-Jun;6(3):1029-35. doi: 10.1021/mp9000487.
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.
高胆固醇水平（即高胆固醇血症）与许多疾病相关，尤其是与冠心病风险有关。普罗布考常用于降低血液中的胆固醇。虽然这种药物的有效性在很大程度上取决于其溶解度，但不幸的是，它几乎不溶于水（在水中的溶解度为5纳克/毫升）。因此，开发提高其溶解度和生物利用度以及增强药物疗效的方法至关重要。在此我们表明，一种新方法提高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普罗布考（PBC）与十二烷基硫酸钠和甲基丙烯酸共聚物一起研磨。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非晶态的转变，并确定了由于研磨过程使其靠近共聚物从而能够形成纳米颗粒。
