RESUMO
Thalidomide is emerging as a therapeutic agent with renewed clinical importance, presenting anti-inflammatory, immunomodulatory, and antineoplasic properties. In this work, we studied the complexation of thalidomide with cyclodextrins as a strategy to circumvent the poor aqueous solubility of the drug. Thalidomide-hydroxypropyl-ß-cyclodextrin complexes were obtained by kneading method and were characterized by differential scanning calorimetry, powder X-ray diffractometry, and scanning electronic microscopy. The aqueous solubility and in vitro dissolution of thalidomide were significantly improved through the complexation. Physicochemical analysis of the complexes in solid state revealed a decreased crystallinity of the complexed drug in comparison with free thalidomide. Thalidomide was able to dissociate from the complexes and permeates across intestinal epithelial Caco-2 cells with a favorable high permeability profile equivalent to that of the free drug. In summary, the present results suggest that thalidomide-hydroxypropyl-ß-cyclodextrin complexes could be regarded as a promising strategy for improving the gastrointestinal absorption of thalidomide.
Assuntos
Absorção Intestinal/fisiologia , Talidomida/síntese química , Talidomida/metabolismo , beta-Ciclodextrinas/síntese química , beta-Ciclodextrinas/metabolismo , 2-Hidroxipropil-beta-Ciclodextrina , Células CACO-2 , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Humanos , Absorção Intestinal/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Solubilidade/efeitos dos fármacos , Talidomida/farmacologia , Difração de Raios X , beta-Ciclodextrinas/farmacologiaRESUMO
Chemical investigation of the roots of Wilbrandia ebracteata Cogn. (Cucurbitaceae) led to the isolation of two new (1- 2) and four known (3- 6) cucurbitacins. Their structures were elucidated by NMR and MS and compared with related compounds. The in vitro cytotoxicity of isolated compounds was evaluated against RD, KB, HCT-8, and A549 cell lines showing strong activity.