title: Inclusion complexes of paclitaxel and oligo(ethylenediamino) bridged bis(beta-cyclodextrin)s: solubilization and antitumor activity.
abstract: The inclusion complexation behavior of paclitaxel with a series of oligo(ethylenediamino) bridged bis(beta-cyclodextrin)s possessing bridge chains in different length (1-4) has been investigated in order to improve the water solubility of paclitaxel. It is found that only the long-tethered bis(beta-cyclodextrin)s 1 and 2 can form the inclusion complexes with paclitaxel, which are characterized by NMR, SEM, XRD, FT-IR, TG-DTA, DSC, and microcalorimetry technology. The results obtained show that bis(beta-cyclodextrin)s 1 and 2 are able to solubilize paclitaxel to high levels up to 2 and 0.9 mg/mL, respectively. The high complex stability of bis(beta-cyclodextrin) 1 and paclitaxel is discussed from thermodynamic viewpoint. Furthermore, the cytotoxicity of these complexes assessed using a human erythroleukemia K562 cell line indicates that the IC(50) value of 1/paclitaxel complex is 6.0 x 10(-10) mol/dm(3) (calculated as paclitaxel molar concentration), which means that the antitumor activity of 1/paclitaxel complex is better than that of parent paclitaxel (IC(50) value 9.8 x 10(-10) mol/dm(3)). This high antitumor activity, along with the satisfactory water solubility and high thermal stability of the 1/paclitaxel complex, will be potentially useful for its clinical application as a highly effective antitumor drug.
authors.affiliation: Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China. yuliu@public.tpt.tj.cn
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Guo-Song
authors.initials: GS
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Cao
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Ge
authors.forename: Ying-Jin
authors.initials: YJ
authors.lastname: Yuan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology; D012995:Solubility / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D047392:beta-Cyclodextrins; C031215:betadex; D017239:Paclitaxel