RESUMEN
The influence of temperature on membrane-prazosin interactions was studied. Prazosin, a quinazoline derivative of 2-furoylpiperazine, is a classic antihypertensive and antiarrhythmic drug. A mixed cholesterol/phospholipid monolayer at the water/air interface was employed as a simplified biomembrane model. Brewster angle microscopy (BAM) was used to visualize the monolayer morphology. It was found that prazosin penetrates Langmuir monolayers and modifies the interactions between membrane components, causing monolayer fluidization. An increase in temperature facilitates penetration of prazosin into the monolayers. Prazosin interacts preferentially with phosphatidylcholine and modifies the morphology of the condensed phase domains of DPPC. In the presence of prazosin, monolayers collapse at lower surface pressures. The difference between the collapse pressures of monolayers on water with and without prazosin increases with temperature.
Asunto(s)
Lípidos de la Membrana/química , Membranas Artificiales , Prazosina/química , 1,2-Dipalmitoilfosfatidilcolina/química , Barrera Hematoencefálica , Colesterol/química , Difusión , Fluidez de la Membrana , Prazosina/farmacocinética , Presión , Propiedades de Superficie , TemperaturaRESUMEN
In this study, the effect of prazosin on the molecular interactions between cholesterol and 1,2-dipalmitoylphosphatidylcholine (DPPC) within a monolayer at an air-water interface was studied. A mixed cholesterol/DPPC monolayer was employed as a model lipid membrane. From a detailed analysis of surface pressure-area isotherms, it was concluded that DPPC and cholesterol were miscible and formed non-ideal monolayers on prazosin solution. The thermodynamic stability of the mixed monolayers was investigated by analyzing the free energy of mixing. It was found that the mixed monolayers were more stable than the single component monolayers. Monolayers spread over a subphase with prazosin were more compressible than those spread on pure water. To quantify the effect of prazosin on the monolayer stability, the Gibbs free energy due to the presence of prazosin in the water subphase was calculated. It was found that prazosin penetrated and destabilized mixed cholesterol/DPPC monolayers. However, a comparison of the drug penetration into the pure DPPC monolayer and the mixed cholesterol/DPPC monolayer showed that the presence of cholesterol in the DPPC monolayer considerably restricted the drug penetration.