title: Evaluation of molecular chaperone drug function: Regorafenib and β-cyclodextrins.
abstract: Regorafenib (RG) was an oral multi-kinase inhibitor with poor water solubility. In order to enhance the drug's solubility, dissolution and bioavailability, the binary molecular chaperone drug between RG and β-cyclodetrin (β-CD) had prepared by co-crystallization. The structure of RG-β-CD was characterized by thermal analysis, powder X-ray diffraction, infrared spectroscopy and nuclear magnetic resonance. Phase-solubility study revealed the higher solubility and complexing ability of β-CDwith RG.The solubility and dissolution of RG-β-CD was significantly enhanced in pH 1.2 medium, pH 6.8 PBS buffer solution and distilled water compared to RG. In vivo distribution and antitumor studies revealed that the bioavailability of RG-β-CD was increased when β-CD mated with RG. Therefore, these findings could provide a suitable pharmaceutical dosage to enhanced therapeutic activity.
authors.affiliation: Chemistry Department, Zhejiang University, Hangzhou, 310028, PR China. Electronic address: huxiurong@zju.edu.cn.
authors.forename: Xiurong
authors.initials: X
authors.lastname: Hu
authors.affiliation: Chemistry Department, Zhejiang University, Hangzhou, 310028, PR China.
authors.forename: Mengying
authors.initials: M
authors.lastname: Sun
authors.affiliation: Chemistry Department, Zhejiang University, Hangzhou, 310028, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Chemistry Department, Zhejiang University, Hangzhou, 310028, PR China. Electronic address: tangguping@zju.edu.cn.
authors.forename: Guping
authors.initials: G
authors.lastname: Tang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018832:Molecular Chaperones / Q000008:administration & dosage / Q000737:chemistry*; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D018832:Molecular Chaperones; D010671:Phenylurea Compounds; D011725:Pyridines; D047392:beta-Cyclodextrins; C559147:regorafenib
keywords: Dissolution; In vivo; Molecular chaperone; Regorafenib; Solubility; β-Cyclodetrin