Preparation, characterization and antitumor effects of cyclodextrin inclusion complexes of regorafenib
10.3785/j.issn.1008-9292.2017.04.05
- VernacularTitle:抗肿瘤药物瑞戈非尼—环糊精包合物的制备及其生物学性质研究
- Author:
Kaihang LIU
1
;
Mengying SUN
;
Guping TANG
;
Xiurong HU
Author Information
1. 浙江大学化学系
- Keywords:
Protein kinase inhibitors;
Beta-cyclodextrins;
Drug compounding;
Antineoplastic agents;
Solubility;
Biological availability
- From:
Journal of Zhejiang University. Medical sciences
2017;46(2):144-152
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To prepare and characterize cyclodextrin inclusion complexes of regorafenib and to investigated their antitumor effects.Methods:Three inclusion complexes (RG-β-CD,RG-γ-CD,RG-Hp-β-CD) were prepared by recrystallization and solvent evaporation methods between regorafenib (RG) and β-cyclodextrin (β-CD),γ-cyclodextrin (γ-CD) and hydroxypropyl-β-cyclodextrin (Hp-β-CD),respectively.The compounds were characterized by Fourier transform infrared spectroscopy (FT-IR),thermogravimetric analysis (TG),differential scanning calorimetry (DSC),powder X-ray diffraction (PXRD),1 H nuclear magnetic resonance (1H-NMR),nuclear overhauser effect spectroscopy (NOESY).Human colon cancer SW620 cells were inoculated to Balb/c-nu nude mice,PBS,RG or RG-β-CD were given orally for 3 weeks,and the volumes of tumor were determined and compared among 3 groups.Results:The solubility and dissolution were improved after inclusion with 3 kinds of cyclodextrins.RG-β-CD had the best stability,followed by RG-γ-CD inclusion.The in vivo study showed that the tumor suppressive effect of RG-β-CD was stronger than that of regorafenib.Conclusion:The bioavailability of regorafenib by inclusion with cyclodextrin is enhanced due to the increased solubility,which can provide an effective method for improving solubility and dissolution of antitumor agents.
