RESUMEN
BACKGROUND: Tamoxifen (Tam) is used for the treatment and prevention of estrogen-receptor-positive human breast and other cancers. Its use in ovarian cancer has not been well studied. METHOD: We formulated and characterized a water-soluble Tam-2-hydroxylpropyl-beta-cyclodextrin (HPbetaCD; 1:2 M) complex. RESULTS: The differential scanning calorimetery of Tam-HPbetaCD indicated the transition of Tam from crystalline to amorphous form on addition of HPbetaCD. (1)H-nuclear magnetic resonance nuclear overhauser effect cross-peaks between phenyl moieties of Tam and HPbetaCD, and downfield shifts in H-3 (0.26) and H-5 (0.29) protons of HPbetaCD suggested the inclusion of Tam in HPbetaCD cavity. Transmission-electron microscopy studies of HPbetaCD and the Tam-HPbetaCD complex revealed the formation of aggregated nanoassembly at 60-180 nm. Dimethyl thiazol diphenyltetrazolium bromide assay demonstrated 7.37 +/- 2.32% cell survival of OAW-42 cells with 3 microg/ml Tam concentration. CONCLUSION: The Tam-HPbetaCD nanoassembly entered the cell owing to enhanced permeability and retention property of tumor cell and antiestrogenic Tam and, therefore, resulted in excellent anticancer efficacy in the ovarian cancer cell line.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Nanoestructuras/química , Neoplasias Ováricas/tratamiento farmacológico , Receptores de Estrógenos/metabolismo , Tamoxifeno/química , Tamoxifeno/uso terapéutico , beta-Ciclodextrinas/química , Antineoplásicos Hormonales/química , Antineoplásicos Hormonales/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Nanotecnología/métodos , Tamoxifeno/farmacologíaRESUMEN
The aim of our studies was to formulate a system that delivers the required radiation dose to the tumor site and minimize the harm to other organs or tissues. The poly (lactic-co-glycolic acid, 75:25; 50:50) microspheric radiation delivery system was fabricated using double emulsion solvent evaporation technique for the encapsulation of technetium-99m(V)dimercaptosuccinic acid ((99m)Tc(V)DMSA). Microspheres of different sizes (0.2-20.0 mum) were prepared. The initial burst in microspheres with 10% and 1% poly vinyl alcohol (PVA) in the presence of poly ethylene glucol (PEG) was as 30% and 16% respectively, however the initial burst in microspheres without the PEG was 9% and 1.2% respectively. The results indicated that smaller microspheres had higher encapsulation (68%) of (99m)Tc(V)DMSA than larger microspheres (15%). The stirring rate changed the surface of the microspheres from smooth spherical, to spherical, porous. The ratio of co-polymers (75:25/50:50) affected the release kinetics. In conclusion, our studies with varied surfactant concentrations, co-polymer concentrations and speed of solvent evaporation, on the morphology and release kinetics of (99m)Tc(V)DMSA from the microspheres, may be applied for the fabrication of targeted radiotherapeutic microspheres by substituting (99m)Tc(V)DMSA with rhenium-188 (V) DMSA ((188)Re(V)DMSA). (188)Re(V)DMSA is a therapeutic analogue of (99m)Tc(V)DMSA and both share similar radiopharmaceutical properties.