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姜黄素-β-环糊精-聚乙烯吡咯烷酮超分子包合物的制备:实验、分子对接及临床前抗炎评估

Formulation of Curcumin-β-cyclodextrin-polyvinylpyrrolidone supramolecular inclusion complex: experimental, molecular docking, and preclinical anti-inflammatory assessment.

作者信息

Jafar Mohammed, Khalid Mohammed Saifuddin, Aldossari Mashael Fehaid Eid, Amir Mohd, Alshaer Fatima Ibrahim, Adrees Fatima Ali Abdullah, Gilani Sadaf Jamal, Alshehri Sultan, Hassan Mohd Zaheen, Imam Syed Sarim

机构信息

Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

出版信息

Drug Dev Ind Pharm. 2020 Sep;46(9):1524-1534. doi: 10.1080/03639045.2020.1810268. Epub 2020 Aug 27.

Abstract

This research planned to ameliorate an aqueous solubility and dissolution of Curcumin CUR) by the formulation of inclusion complex with β-cyclodextrin (β-CD) and polyvinylpyrrolidone (PVP). The phase solubility study was performed to assess the solubility of CUR. The prepared CUR complex assessed for dissolution study, physicochemical evaluation, antioxidant activity, molecular modeling, and anti-inflammatory assessment. The pivotal findings of phase-solubility studies demonstrate apparent stability constant (Kc) and complexation efficiency (CE) values for CUR-β-CD and CUR-β-CD-PVP complex was 175.4  , 1.15% and 833.3.2 and 5.21%, respectively. The characterization results revealed amorphization of crystalline state (CUR) into amorphous state. The maximum drug release found with the ternary CUR complex (F7), i.e. 45.41 ± 3.78% in 6 h study. The chemical shift in the NMR supports that the aromatic ring of CUR is completely complexed inside the β-CD cavity. The antioxidant activity of pure CUR was found to be 58.02 ± 2.21% and CUR ternary complex (F7) showed significantly higher activity to 96.02 ± 2.46%. The effect of CUR complex (F7) was also found significantly higher than that of pure CUR. The molecular modeling study depicted that PVP increased the stability of the ternary complex by forming the link between CUR and β-CD. Thus, the ternary inclusion complex of CUR-β-CD-PVP could contribute as an innovative outcome in the enhancement of solubility and activity.

摘要

本研究计划通过制备姜黄素(CUR)与β-环糊精(β-CD)和聚乙烯吡咯烷酮(PVP)的包合物来改善姜黄素的水溶性和溶出度。进行相溶解度研究以评估CUR的溶解度。对制备的CUR复合物进行溶出度研究、理化评价、抗氧化活性、分子模拟和抗炎评估。相溶解度研究的关键结果表明,CUR-β-CD和CUR-β-CD-PVP复合物的表观稳定常数(Kc)和络合效率(CE)值分别为175.4、1.15%和833.3、5.21%。表征结果显示结晶态(CUR)转变为无定形态。在三元CUR复合物(F7)中发现最大药物释放量,即在6小时研究中为45.41±3.78%。核磁共振中的化学位移支持CUR的芳香环完全络合在β-CD腔内。发现纯CUR的抗氧化活性为58.02±2.21%,CUR三元复合物(F7)表现出显著更高的活性,为96.02±2.46%。还发现CUR复合物(F7)的效果明显高于纯CUR。分子模拟研究表明,PVP通过在CUR和β-CD之间形成连接来提高三元复合物的稳定性。因此,CUR-β-CD-PVP三元包合物可能是提高溶解度和活性方面的一项创新成果。

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