School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Mater Sci Eng C Mater Biol Appl. 2019 Oct;103:109737. doi: 10.1016/j.msec.2019.109737. Epub 2019 May 10.
In this study, twisted rod-like chiral mesoporous silicas (CMSs) with discriminating chiral characteristics (D/L) were designed and biomimetic synthesized by using L- and d-alanine derivatives as templates, and employed as poorly water-soluble chiral drug ibuprofen (IBU) carriers. The morphology and mesoscopic characteristics of CMSs were determined by transmission electron microscope (TEM) and small-angle X-ray scattering (SAXS). Meanwhile, the physicochemical properties of CMSs before and after drug loading were systematically characterized by infrared spectroscopy (IR), nitrogen adsorption, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and induced circular dichroism (ICD). The results suggested that, the CMSs exhibited local chiral characteristics, which were successfully endowed by the alanine-derivative surfactants templates with a reversal of chirality. The crystalline state of IBU was effectively converted to amorphous state after being incorporated into CMSs, and the drug delivery systems shared the chiral characteristic of carriers. Besides, in vitro drug release experiments were respectively performed in simulated gastric fluid (SGF, pH 1) and simulated intestinal fluid (SIF, pH 6.8) medium, and the results demonstrated that both l-CMS and d-CMS could improve the dissolution of IBU in SGF medium, which could be explained by the amorphization of IBU. Particularly, due to the different pore geometry of these two materials, CMSs with different chirality (D/L) could be applied as carriers to accomplish drug release differentiation.
在这项研究中，设计并仿生合成了具有手性识别特性（D/L）的扭曲棒状手性介孔硅（CMSs），以 L-和 d-丙氨酸衍生物为模板，并用作疏水性手性药物布洛芬（IBU）的载体。通过透射电子显微镜（TEM）和小角 X 射线散射（SAXS）确定了 CMSs 的形态和介观特征。同时，通过红外光谱（IR）、氮气吸附、X 射线衍射（XRD）、差示扫描量热法（DSC）和诱导圆二色性（ICD）系统地表征了 CMSs 载药前后的物理化学性质。结果表明，CMSs 表现出局部手性特征，这是通过具有手性反转的丙氨酸衍生物表面活性剂模板成功赋予的。IBU 的晶态在被包埋到 CMSs 中后有效地转化为无定形态，并且药物传递系统具有载体的手性特征。此外，在模拟胃液（SGF，pH 1）和模拟肠液（SIF，pH 6.8）介质中分别进行了体外药物释放实验，结果表明，l-CMS 和 d-CMS 均可提高 IBU 在 SGF 介质中的溶解度，这可以通过 IBU 的无定形化来解释。特别地，由于这两种材料的孔几何形状不同，具有不同手性（D/L）的 CMSs 可以用作载体来实现药物释放的差异。
