RESUMEN
Diabetic retinopathy is the leading cause of blindness, yet its treatment is very limited. Anti-VEGF drug has been widely applied in ocular disease, but its effects on diabetic retinopathy and the underlying mechanism have remained to be fully explored. To elucidate the role of anti-VEGF treatment, we sought to determine the effects of bevacizumab on diabetic neurovascular changes extending from the 3rd to 9th week with induced diabetes in adult rats. The retinal neurovascular changes included increased expression of VEGF, nNOS, iNOS, eNOS, and NO in the course of diabetes progression. In diabetic rats given bevacizumab injection, the ganglion cell loss and alterations of retinal thickness were ameliorated. In this connection, the immunofluorescence labeling of the above biomarkers was noticeably decreased. Along with this, Western blotting confirmed that bevacizumab treatment was associated with a decrease of VEGF, Flk-1, and cAMP response element binding and protein kinase C protein expression. The present results suggest that bevacizumab treatment in the early stage of the retinopathy may ameliorate the lesions of retinopathy, in which VEGF/Flk-1 signaling has been shown here to play an important role.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Retinopatía Diabética/tratamiento farmacológico , Inhibidores de la Angiogénesis/administración & dosificación , Animales , Bevacizumab/administración & dosificación , Diabetes Mellitus Experimental/metabolismo , Retinopatía Diabética/metabolismo , Inyecciones Intravítreas , Masculino , Ratas , Ratas Sprague-Dawley , Retina/efectos de los fármacos , Retina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Objective: To study the pharmacokinetic and tissue distribution of quercetin injection and submicron emulsion after intravenous administration in mice. Methods: The concentration of quercetin in mice plasma and tissues were determined by RPHPLC. Results: Liver had the highest tissue concentration of quercetin submicron emulsion, followed by plasma, kidney, spleen, lung, heart and brain. And their had significantly increased compared with the AUC0âtof plasma, liver, spleen, kidney and brain after administration of quercetin injection( P < 0. 05). The Rte and Re of liver, brain and spleen were all larger than 1. Conclusion: Quercetin submicron emulsion significantly alters the plasma pharmacokinetic characteristics of quercetin after intravenous administration in mice. And it has good targeting location features in liver, brain, spleen and kidney.
Asunto(s)
Hígado , Distribución Tisular , Animales , Encéfalo , Emulsiones , Riñón , Pulmón , Ratones , Especificidad de Órganos , Quercetina , BazoRESUMEN
OBJECTIVE: To prepare curcumin nanosuspensions (Cur-NS), and to study the pharmacokinetics of Cur-NS in rats. METHODS: Cur-NS was prepared by the high pressure homogenization technology. The particle size, PdI and Zeta electric potential of nanosuspensions were taken as the indexes to determinate the factors that influenced the preparation process greatly. Curcumin concentrations in plasma were determined by HPLC and the pharmacokinetic parameters were calculated. RESULTS: The particle size, polydisper- sion index, Zeta potential of Cur-NS were found to be 396. 4 ± 67. 2 nm, 0. 369 ± 0. 061 and -16.7 ± 3. 5 mV,respectively. AUC(0-t) of curcumin bulk drugs and Cur-NS were estimated to be 3. 62 ± 0. 66 mg/(L . h) and 14. 36 ± 1. 20 mg/( L . h), half lifes(t1/2) were 0. 62 ± 0. 06 h and 2. 15 ± 0. 15 h tmax were 1. 83 ± 0. 11 h and 1. 02 ± 0. 09 h, Cmax were 0. 94 ± 0.12 mg/L and 5. 78 ± 0. 46 mg/L, respectively. CONCLUSION: The pharmacokinetic results demonstrate that the curcumin bulk drugs prepared into Cur-NS can increase the drug's bioavailability in rats significantly.
Asunto(s)
Curcumina/farmacocinética , Portadores de Fármacos , Animales , Disponibilidad Biológica , Nanopartículas/administración & dosificación , Tamaño de la Partícula , RatasRESUMEN
OBJECTIVE: To develop a procedure for preparing paclitaxel encapsulated PEGylated liposomes. METHODS: The membrane hydration followed extraction method was used to prepare PEGylated liposomes. The process and formulation variables were optimized by "Box-Behnken Design (BBD)" of response surface methodology (RSM) with the amount of Soya phosphotidylcholine (SPC) and PEG2000-DSPE as well as the rate of SPC to drug as independent variables and entrapment efficiency as dependent variables for optimization of formulation variables while temperature, pressure and cycle times as independent variables and particle size and polydispersion index as dependent variables for process variables. The optimized liposomal formulation was characterized for particle size, Zeta potential, morphology and in vitro drug release. RESULTS: For entrapment efficiency, particle size, polydispersion index, Zeta potential, and in vitro drug release of PEGylated liposomes was found to be 80.3%, (97.15 ± 14.9) nm, 0.117 ± 0.019, (-30.3 ± 3.7) mV, and 37.4% in 24 h, respectively. The liposomes were found to be small, unilamellar and spherical with smooth surface as seen in transmission electron microscopy. CONCLUSION: The Box-Behnken response surface methodology facilitates the formulation and optimization of paclitaxel PEGylated liposomes.