Corrêa Daniel H A, Melo Patricia S, de Carvalho Carlos A A, de Azevedo Mariângela B M, Durán Nelson, Haun Marcela
Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, Campinas, SP 13083-970, Brazil.
Eur J Pharmacol. 2005 Mar 7;510(1-2):17-24. doi: 10.1016/j.ejphar.2005.01.016.
Trans-dehydrocrotonin has antiulcerogenic and antitumor activities. A complex of beta-cyclodextrin with dehydrocrotonin was developed to improve the delivery of dehydrocrotonin. Complex in solid state was evaluated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and scanning electron microscopy (SEM). X-ray diffraction and scanning electron microscopy studies showed that dehydrocrotonin exists in a semicrystalline state in the complexed form with beta-cyclodextrin. Differential scanning calorimetry studies showed the existence of a complex of dehydrocrotonin with beta-cyclodextrin. The thermal gravimetric analysis studies confirmed the differential scanning calorimetry results of the complex. Free dehydrocrotonin and the dehydrocrotonin/beta-cyclodextrin inclusion complex were assayed in freshly isolated rat hepatocytes and in V79 cells. Cytotoxicity was determined using nucleic acid content, methylthiazoletetrazolium (MTT) reduction and neutral red uptake assays. In all assays, there was a large reduction (3.5-16.1-fold) in the cytotoxicity of dehydrocrotonin in hepatocytes when complexed with beta-cyclodextrin, whereas for V79 cells the decrease in cytotoxicity was 1.7- and 1.87-fold for MTT reduction and nucleic acid content assays, respectively. The lower cytotoxicity of the dehydrocrotonin/beta-cyclodextrin complex compared to free dehydrocrotonin in rat hepatocytes and V79 cells suggests that such a complex may be useful for the administration of dehydrocrotonin in vivo.
反式脱氢巴豆素具有抗溃疡和抗肿瘤活性。开发了一种β-环糊精与脱氢巴豆素的复合物以改善脱氢巴豆素的递送。使用X射线衍射（XRD）、差示扫描量热法（DSC）、热重分析（TGA）和扫描电子显微镜（SEM）对固态复合物进行了评估。X射线衍射和扫描电子显微镜研究表明，脱氢巴豆素以与β-环糊精复合的形式存在于半结晶状态。差示扫描量热法研究表明存在脱氢巴豆素与β-环糊精的复合物。热重分析研究证实了该复合物的差示扫描量热法结果。在新鲜分离的大鼠肝细胞和V79细胞中测定了游离脱氢巴豆素和脱氢巴豆素/β-环糊精包合物。使用核酸含量、甲基噻唑基四氮唑（MTT）还原和中性红摄取试验测定细胞毒性。在所有试验中，与β-环糊精复合时，脱氢巴豆素在肝细胞中的细胞毒性大幅降低（3.5至16.1倍），而对于V79细胞，MTT还原试验和核酸含量试验的细胞毒性降低分别为1.7倍和1.87倍。脱氢巴豆素/β-环糊精复合物在大鼠肝细胞和V79细胞中的细胞毒性低于游离脱氢巴豆素，这表明这种复合物可能有助于脱氢巴豆素的体内给药。
