Du Hongliang, Liu Mengrui, Yang Xiaoye, Zhai Guangxi
Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
J Colloid Interface Sci. 2015 Dec 15;460:87-96. doi: 10.1016/j.jcis.2015.08.049. Epub 2015 Aug 24.
Quercetin (QC), a type of plant-based chemical, has been reported to own anticancer activity in vivo. However, the poor water solubility limits its pharmaceutical application. In this study, two kinds of QC-loaded self-aggregates based on O-carboxymethyl chitosan-cholic acid conjugates (CMCA) were developed to improve the drug bioavailability in which glycyrrhetinic acid (GA) modification was utilized in the nanocarrier fabrication (QC-GA-CMCA) or not (QC-CMCA). These self-aggregates were prepared by a modified ultrasound-dialysis method and the role of GA modification on the evaluation of QC-loaded self-aggregates was investigated. Transmission Electron Microscopy (TEM) images revealed the formation of spherical particles of both self-aggregates. Dynamic Light Scattering (DLS) analysis and UV-VIS spectroscopy showed that the QC-GA-CMCA had smaller size, narrower size distribution, higher drug loading and entrapment efficiency than corresponding QC-CMCA aggregates. QC-GA-CMCA showed more obvious sensitivity to acidic pH condition based on the zeta potential measurements at various pHs, and fastest drug release was observed at pH 5.7 for QC-CMCA while at pH 6.5 for QC-GA-CMCA. In addition, QC-GA-CMCA demonstrated enhanced cell cytotoxicity and higher cell apoptosis rate in vitro, and also higher AUC value and a prolonged residence time of drug in vivo.
槲皮素（QC）是一种植物源化学物质，据报道在体内具有抗癌活性。然而，其 poor 水溶性限制了其药物应用。在本研究中，开发了两种基于 O-羧甲基壳聚糖-胆酸共轭物（CMCA）的载 QC 自聚集体，以提高药物生物利用度，其中在纳米载体制备中使用了甘草次酸（GA）修饰（QC-GA-CMCA）或未使用（QC-CMCA）。这些自聚集体通过改良的超声透析法制备，并研究了 GA 修饰对载 QC 自聚集体评估的作用。透射电子显微镜（TEM）图像显示两种自聚集体均形成球形颗粒。动态光散射（DLS）分析和紫外可见光谱表明，QC-GA-CMCA 比相应的 QC-CMCA 聚集体具有更小的尺寸、更窄的尺寸分布、更高的载药量和包封率。基于不同 pH 下的 zeta 电位测量，QC-GA-CMCA 对酸性 pH 条件表现出更明显的敏感性，QC-CMCA 在 pH 5.7 时观察到最快的药物释放，而 QC-GA-CMCA 在 pH 6.5 时观察到最快的药物释放。此外，QC-GA-CMCA 在体外表现出增强的细胞毒性和更高的细胞凋亡率，在体内也具有更高的 AUC 值和更长的药物驻留时间。
