RESUMEN
Phospholipid and non-phospholipid vesicles are extensively studied as drug delivery systems to modify pharmacokinetics of drugs and to improve their action in target cells. It is believed that the major barrier to efficient drug delivery is entrapment of drugs in the endosomal compartment, since this eventually leads to its degradation in lysosomes. For these reasons, the knowledge of internalization pathway plays a fundamental role in optimizing drug targeting. The aim of this work is to characterize pH-sensitive Tween 20 vesicles, their interaction with macrophage-like cells and their comparison with pH-sensitive liposomes. The effect of different amounts of cholesteryl hemissucinate on surfactant vesicle formation and pH-sensitivity was studied. To evaluate the initial mode of internalization in Raw 264.7 and the intracellular fate of neutral and pH-sensitive formulations, flow cytometry in presence and in absence of selected inhibitors and fluorescence microscopy in absence and presence of specific fluorescent endocytotic markers were used. The obtained results showed that the surfactant vesicle pH-sensitivity was about two or three fold higher than that obtained with pH-sensitive liposomes in the presence of serum in vitro. The uptake mechanism of surfactant vesicles, after incubation with macrophage-like cells, is comparable to that of liposomes (clathrin-mediated endocytosis).
Asunto(s)
Endocitosis/fisiología , Macrófagos/metabolismo , Fosfolípidos/farmacocinética , Polisorbatos/farmacocinética , Tensoactivos/farmacocinética , Animales , Transporte Biológico/efectos de los fármacos , Fenómenos Biofísicos , Línea Celular , Vesículas Citoplasmáticas/química , Vesículas Citoplasmáticas/metabolismo , Endocitosis/efectos de los fármacos , Fluoresceínas/metabolismo , Colorantes Fluorescentes/metabolismo , Concentración de Iones de Hidrógeno , Liposomas/química , Liposomas/metabolismo , Liposomas/farmacocinética , Ratones , Microscopía Fluorescente , Fosfolípidos/química , Fosfolípidos/metabolismo , Polisorbatos/metabolismo , Polisorbatos/farmacología , Tensoactivos/metabolismo , Tensoactivos/farmacologíaRESUMEN
This report deals with a new procedure suitable for the extraction of coumarin 1 from Mikania glomerata. The aim of this investigation is to obtain this compound in an economically profitable way, taking into account the yield of its extraction, the cost, and the time of the overall process. Fresh and dried plants collected in several areas of the State of Rio de Janeiro were used, and seasonal effects on coumarin content were studied. Obtained results indicated that extraction with a 1% (w/v) NaOH solution, under appropriate conditions, allows a simple and complete recovery of the desired product and that the best yields were obtained with the fresh aerial parts of the plant. Season and area of harvesting effects have also been studied.
Asunto(s)
Cumarinas/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Costos y Análisis de Costo , Industria Farmacéutica/economía , Estaciones del Año , Hidróxido de Sodio/químicaRESUMEN
Bile acids have been absorbed on a microporous polypropylene membrane and the diffusion of ionic and non-ionic compounds through the barriers obtained has been studied at different pH values. Results indicate that permeation rates are affected by environmental pH conditions and an explanation of this behaviour is proposed. This study represents an approach for a pH-controlled drug delivery system.