RESUMO
Valsartan [VAL] shows poor oral bioavailability mainly as a result of its low water solubility at low pH. This study is designed to investigate the dissolution properties and physicochemical characteristics of novel PVP-based solid dispersions [SDs] containing VAL. The SDs were prepared with polyvinylpyrrolidone [PVP-K30] as a hydrophilic polymer, sodium hydroxide [NaOH] as an alkalizer, and poloxamer 188 [F68] as a surfactant, without using any organic solvents by a freeze-drying method. The dissolution study was carried out and the physicochemical properties of SDs were also characterized by using differential scanning calorimetry [DSC], fourier transform-infrared [FT-IR] spectroscopy, X-ray diffractometry [XRD] and scanning electron microscopy [SEM]. The dissolution rates of SDs were significantly improved at pH 1.2 and pH 6.8 compared to that of pure drug. The results of physicochemical properties suggested that some interactions between VAL and carriers had occurred in the molecular level and the drug presented in the SDs was amorphous. It was concluded that the novel PVP-based SDs has been successfully prepared by a freeze-drying method, resulting in significant dissolution improvement of VAL
Assuntos
Valina/análogos & derivados , Liofilização , Liberação Controlada de Fármacos , Técnicas In Vitro , Povidona , Fenômenos QuímicosRESUMO
Emerging evidence indicates that ischemic preconditioning (IPC) induces autophagy which attenuates myocardial ischemia/reperfusion (I/R) injury. However, the precise mechanisms remain complex and unclear. The present study was to investigate which autophagy pathway was involved in the cardioprotection induced by IPC, so that we can acquire an attractive treatment way for ischemic heart disease. Adult male Sprague-Dawley (SD) rats were randomly divided into sham group, I/R group and IPC group. IPC was induced with three cycles of 5 min regional ischemia alternating with 5 min reperfusion in a heart I/R model. Samples were taken from the center of the infracted heart and examined by using the electron microscopy, the terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) method, Western blotting and co-immunoprecipitation (Co-IP). A large number of autophagic vacuoles were observed in the cardiomyocytes of IPC group as compared with I/R group. LC3-II formation, an autophagy marker, was up-regulated in IPC group as compared with I/R group (P<0.05). Moreover, the interaction between Beclin 1 and Bcl-2 was significantly increased in IPC group as compared with I/R group (P<0.01). It was also found that IPC decreased I/R-induced apoptosis (P<0.01). These results suggest that IPC inhibits Beclin 1-dependent excessive autophagy in reperfusion phase and cooperates with anti-apoptosis pathway to diminish the cell death induced by the myocardial I/R injury.
RESUMO
Emerging evidence indicates that ischemic preconditioning (IPC) induces autophagy which attenuates myocardial ischemia/reperfusion (I/R) injury. However, the precise mechanisms remain complex and unclear. The present study was to investigate which autophagy pathway was involved in the cardioprotection induced by IPC, so that we can acquire an attractive treatment way for ischemic heart disease. Adult male Sprague-Dawley (SD) rats were randomly divided into sham group, I/R group and IPC group. IPC was induced with three cycles of 5 min regional ischemia alternating with 5 min reperfusion in a heart I/R model. Samples were taken from the center of the infracted heart and examined by using the electron microscopy, the terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) method, Western blotting and co-immunoprecipitation (Co-IP). A large number of autophagic vacuoles were observed in the cardiomyocytes of IPC group as compared with I/R group. LC3-II formation, an autophagy marker, was up-regulated in IPC group as compared with I/R group (P<0.05). Moreover, the interaction between Beclin 1 and Bcl-2 was significantly increased in IPC group as compared with I/R group (P<0.01). It was also found that IPC decreased I/R-induced apoptosis (P<0.01). These results suggest that IPC inhibits Beclin 1-dependent excessive autophagy in reperfusion phase and cooperates with anti-apoptosis pathway to diminish the cell death induced by the myocardial I/R injury.