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1.
Pharm Res ; 29(7): 1775-86, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22322899

RESUMEN

PURPOSE: Several formulations have been proposed to improve the systemic delivery of novel cancer therapeutic compounds, including cyclodextrin derivatives. We aimed to synthesize and characterize of CDF-ß-cyclodextrin inclusion complex (1:2) (CDFCD). METHODS: The compound was characterized by Fourier transform infrared, differential scanning calorimetry, powder X-ray diffraction studies, H1 & C13 NMR studies and scanning electron microscopic analysis. Its activity was tested against multiple cancer cell lines, and in vivo bioavailability was checked. RESULTS: CDF-ß-cyclodextrin was found to lower IC(50) value by half when tested against multiple cancer cell lines. It preferentially accumulated in the pancreas, where levels of CDF-ß-cyclodextrin in mice were 10 times higher than in serum, following intravenous administration of an aqueous CDF-ß-cyclodextrin preparation. CONCLUSIONS: Novel curcumin analog CDF preferentially accumulates in the pancreas, leading to its potent anticancer activity against pancreatic cancer cells. Synthesis of such CDF-ß-cyclodextrin self-assembly is an effective strategy to enhance its bioavailability and tissue distribution, warranting further evaluation for CDF delivery in clinical settings for treatment of human malignancies.


Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/química , Curcumina/análogos & derivados , Curcumina/administración & dosificación , Portadores de Fármacos/química , Neoplasias Pancreáticas/tratamiento farmacológico , beta-Ciclodextrinas/química , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Curcuma/química , Curcumina/farmacocinética , Curcumina/farmacología , Femenino , Halogenación , Humanos , Ratones , Modelos Moleculares , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Solubilidad
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