RESUMEN
Residue of azole antifungals in the environment is of concern due to the environmental risks and persistence. Distribution, behavior, and fate of frequently used azole antifungal pharmaceuticals were investigated in wastewater at two sewage treatment plants (STPs) in China. Fluconazole, clotrimazole, econazole, ketoconazole, and miconazole were constantly detected at 1-1834 ng L(-1) in the wastewater. The latter four were also ubiquitously detected in sewage sludge. Fluconazole passed through treatment in the STPs and largely remained in the final effluent. On the contrary, biotransformation and sorption to sludge occurred to the other azoles. Ketoconazole was more readily bio-transformed, whereas clotrimazole, econazole, and miconazole were more likely to be adsorbed onto and persisted in sewage sludge. Lipophilicity plays the governing role on adsorption. The highest concentrations in the raw wastewater were observed in winter for the azole pharmaceuticals except for fluconazole. The seasonal difference was smoothed out after treatment in the STPs.
Asunto(s)
Antifúngicos/análisis , Azoles/análisis , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/análisis , Antifúngicos/química , Azoles/química , Biodegradación Ambiental , China , Clotrimazol/análisis , Clotrimazol/química , Econazol/análisis , Econazol/química , Monitoreo del Ambiente , Fluconazol/análisis , Fluconazol/química , Cetoconazol/análisis , Cetoconazol/química , Miconazol/análisis , Miconazol/química , Aguas del Alcantarillado/química , Contaminantes Químicos del Agua/químicaRESUMEN
Topical application of the drugs at the pathological sites offers potential advantages of delivering the drug directly to the site of action. The main aim of this work was to formulate and evaluate Miconazole nitrate (MN) loaded solid lipid nanoparticles (SLN) for topical application. MN-loaded SLN were prepared by modified solvent injection method and characterized for shape, surface morphology, particle size, and drug entrapment. These solid lipid nanoparticles were spherical in shape with smooth surface and possessed mean average size of 206.39 +/- 9.37 nm. In vitro drug release of MN-loaded SLN-bearing hydrogel was compared with MN suspension and MN hydrogel; MN-loaded SLN-bearing hydrogel depicted a sustained drug release over a 24-h period. Tape stripping experiments demonstrated 10-fold greater retention with MN-loaded SLN-bearing hydrogel as compared to MN suspension and MN hydrogel. The in vivo studies were performed by infecting the rats with candida species. It was observed that MN-loaded SLN-bearing hydrogel was more efficient in the treatment of candidiasis. Results indicate that MN-loaded SLN-bearing hydrogel provides a sustaining MN topical effect as well as quicker relief from fungal infection.
Asunto(s)
Antifúngicos/administración & dosificación , Sistemas de Liberación de Medicamentos , Lecitinas/química , Miconazol/administración & dosificación , Nanopartículas/química , Triglicéridos/química , Acrilatos/efectos adversos , Acrilatos/química , Administración Cutánea , Animales , Antifúngicos/análisis , Antifúngicos/farmacocinética , Antifúngicos/uso terapéutico , Candida albicans/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Fenómenos Químicos , Dermatomicosis/tratamiento farmacológico , Composición de Medicamentos , Hidrogeles , Lecitinas/efectos adversos , Masculino , Miconazol/análisis , Miconazol/farmacocinética , Miconazol/uso terapéutico , Nanopartículas/efectos adversos , Nanopartículas/ultraestructura , Conejos , Ratas , Ratas Sprague-Dawley , Piel/efectos de los fármacos , Piel/metabolismo , Pruebas de Irritación de la Piel , Triglicéridos/efectos adversosRESUMEN
Concentrations of six pharmaceutical antimycotics were determined in the sewage water, final effluent and sludge of five Swedish sewage treatment plants (STPs) by solid phase extraction, liquid/solid extraction, and liquid chromatography-electrospray tandem mass spectrometry. The antimycotics were quantified by internal standard calibration. The results were used to estimate national flows that were compared to predictions based on sales figures. Fluconazole was the only one of the six investigated antimycotics that was detected (at concentrations ranging from 90 to 140 ng L(-1)) in both raw sewage water and final effluent. Negligible amounts of this substance were removed from the aqueous phase, and its levels were below the limit of quantification in all of the analyzed sludge samples. In contrast, clotrimazole, ketoconazole and econazole were present in all of the sludge samples, at concentrations ranging between 200 and 1000 microg kg(-1), dry weight. There were close correlations between the national measured and predicted antimycotic mass flows. Antimycotic fate analysis, based on sales figures, indicated that 53% of the total amount of fluconazole sold appeared in the final effluents of the STPs, while 1, 155, 35, 209 and 41% of the terbinafine, clotrimazole, ketoconazole, econazole and miconazole sold appeared in the digested dewatered sludge.