College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China.
Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
AAPS PharmSciTech. 2019 Jul 8;20(6):244. doi: 10.1208/s12249-019-1397-9.
Cyclodextrin (CD) inclusions are generally used to increase the solubility of poorly soluble drugs. In this study, magnolol (MAG) was used as a model drug for exploring the effects of CD on the degradation of pharmaceutical drugs by intestinal microflora. MAG/β-cyclodextrin (β-CD) and MAG/hydroxypropyl-β-CD (HP-β-CD) inclusion complexes were successfully prepared by the saturated aqueous solution and freeze-drying methods, respectively. Structural characterisation along with analyses of solubility, residual water content and drug content of the inclusion complexes was performed. The intestinal microflora of male rats was used to study MAG degradation in vitro. At three concentrations, the degradation of both the inclusion complexes was slower than that of the MAG monomer, MAG and CD mixtures and the MAG-poloxamer 188 micelle. There were no statistically significant differences in the degradation of the MAG/β-CD and MAG/HP-β-CD inclusion complexes. A simulation first-order equation of the degradation parameters revealed that the degradation of the inclusion complexes was slower and pronounced, judging by slope. The experimental findings were verified by molecular docking for predicting the stable molecular structure of the inclusion complexes. In conclusion, the inclusion complexes partially protected MAG from degradation by the intestinal bacteria.
环糊精(CD)包合物通常用于提高难溶性药物的溶解度。在这项研究中,我们以厚朴酚(MAG)为模型药物,探讨了 CD 对肠道微生物降解药物的影响。通过饱和水溶液法和冷冻干燥法成功制备了 MAG/β-环糊精(β-CD)和 MAG/羟丙基-β-环糊精(HP-β-CD)包合物,并对其进行了结构表征以及溶解度、残余水分含量和包合物药物含量的分析。采用雄性大鼠肠道微生物体外研究 MAG 的降解情况。在三个浓度下,两种包合物的降解速度均比 MAG 单体、MAG 和 CD 混合物以及 MAG-泊洛沙姆 188 胶束的降解速度慢。MAG/β-CD 和 MAG/HP-β-CD 包合物的降解没有统计学差异。降解参数的模拟一级方程表明,根据斜率判断,包合物的降解速度较慢且明显。实验结果通过分子对接进行了验证,以预测包合物的稳定分子结构。综上所述,包合物部分保护了 MAG 免受肠道细菌的降解。