人参皂苷CK-乳铁蛋白固体分散体的构建及形成机制

Preparation of ginsenoside CK-lactoferrin solid dispersion and study on formation mechanism

目的探讨人参皂苷CK-乳铁蛋白固体分散体(G-CK-Lf SD)的构建及形成机制。方法以乳铁蛋白(Lf)为载体、人参皂苷CK(G-CK)为主药,构建得到G-CK-Lf SD,采用差示扫描量热(DSC)、X射线衍射(XRD)、扫描电子显微镜(SEM)及体外溶出等方法对所得固体分散体进行表征,辅以分子模拟对其构建机制进行阐述。结果DSC和XRD分析结果显示,G-CK主要以无定形存在于固体分散体中;SEM结果表明,药物以无定形分散附着于Lf载体材料的表面;体外溶出度测定结果表明,G-CK-Lf SD分别在模拟人胃液(pH 1.2)和肠液(pH 6.8)环境下,均存在促进G-CK溶出的功能。分子对接阐述机制表明,Lf表面有6个主要位点与G-CK进行结合,结合能在6.5~8.5 kcal·mol^-1范围内。结论构建得到G-CK-Lf SD,其中G-CK主要以无定形存在,可有效促进其溶出,G-CK与Lf主要通过氢键和疏水作用结合,达到能量和形状的匹配,本研究结果为Lf在固体分散载体领域的应用提供了新思路。

Objective To investigate the preparation of ginsenoside CK-lactoferrin solid dispersion(G-CK-Lf SD)and study on the formation mechanism.Methods G-CK-Lf SD was constructed with lactoferrin(Lf)as the carrier and ginsenoside CK(G-CK)as the main drug.Differential scanning calorimetry(DSC),X-ray diffraction(XRD),scanning electron microscopy(SEM)and in vitro dissolution were used to characterize the solid dispersion,and the construction mechanism was described by molecular simulation.Results DSC and XRD analysis indicated that G-CK in the solid dispersion mainly existed in amorphous form.SEM showed that G-CK as amorphous form was attached to the surface of lactoferrin.The results of in vitro dissolution showed that G-CK-Lf SD could promote the dissolution of G-CK in simulated gastric juice(pH 1.2)and intestinal juice(pH 6.8),respectively.Molecular docking technology demonstrated that lactoferrin had 6 major points which could bind to G-CK.The binding energies were ranged from 6.5 to 8.5 kcal·mol^-1.Conclusion The G-CK-Lf SD,in which G-CK mainly existed as amorphous form,can effectively promote dissolution rate.The combination of G-CK and Lf was mainly because of hydrogen bonding and hydrophobic action,making the matching of energy and shape.Our study provides a new idea for applying Lf as carriers in solid dispersion research.