In vitro and in vivo evaluation of didymin cyclodextrin inclusion complexes: characterization and chemosensitization activity

• Published in: Drug delivery Vol. 27; no. 1; pp. 54 - 65
• Main Authors: Yao, Qing, Lin, Meng-Ting, Lan, Qing-Hua, Huang, Zhi-Wei, Zheng, Ya-Wen, Jiang, Xue, Zhu, Yin-Di, Kou, Longfa, Xu, He-Lin, Zhao, Ying-Zheng
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2020; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin - chemistry; 2-hydroxypropyl-β-cyclodextrin; Animals; Aqueous solutions; beta-Cyclodextrins - chemistry; Bioavailability; Calorimetry, Differential Scanning; Cancer therapies; chemosensitization; Chemotherapy; Didymin; Drug resistance; Flavonoids; Flavonoids - administration & dosage; Flavonoids - pharmacokinetics; Flavonoids - pharmacology; Fruits; Glycosides - administration & dosage; Glycosides - pharmacokinetics; Glycosides - pharmacology; Human Umbilical Vein Endothelial Cells; Humans; inclusion complex; Male; MCF-7 Cells; multidrug resistance; Multidrug resistant organisms; PC12 Cells; Pharmaceutical sciences; Phytochemicals; Rats; Solubility; Spectroscopy, Fourier Transform Infrared; Technology, Pharmaceutical - methods; X-Ray Diffraction; 2-hydroxypropyl-β-cyclodextrin; inclusion complex; multidrug resistance; chemosensitization; Didymin
• ISSN: 1071-7544; 1521-0464; 1521-0464
• DOI: 10.1080/10717544.2019.1704941

Didymin is a dietary flavonoid that first found in citrus fruits, and possesses antioxidant properties. Our preliminary experiments first discovered that didymin was able to sensitize the resistant cancer cells against chemotherapeutics and combat multidrug resistance. However, its poor aqueous solubility and resultant low bioavailability limit its potentials as an adjuvant phytochemical drug for chemotherapy. Thus, this study prepared the inclusion complex of didymin with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin to improve its bioavailability and then evaluate their chemosensitization effects. The didymin inclusion complexes formulation was prepared and their host-guest structure was characterized by FT-IR, PXRD, DSC, and SEM techniques. In vitro/in vivo results demonstrated that didymin inclusion complex enhanced its water solubility and orally bioavailability. Furthermore, didymin inclusion complex exerted considerable chemosensitivity potency, and improve the anti-tumor effects of chemotherapeutics in vivo. Therefore, didymin inclusion complex could provide a safe, effective, economical, and adjuvant drug for future treatment of chemoresistant cancers.