Effects of absorption enhancer surfactants on culture models of intestinal and vascular barriers

摘要: Surfactants used in pharmaceutical products have several advantageous properties; they improve drug absorption and dissolution, protect active molecules. However, adverse effects are also observed during the application of different surface agents which necessitates investigation registered surfactants novel enhancer candidates. Cremophor RH40 EL widely excipients oral intravenous formulations. Studies indicate that Cremophors, especially EL, toxic side effects, but few data available on endothelial epithelial cells form biological barriers directly exposed to these In our human intestinal vascular were treated with Cremophor clinically relevant concentrations their effect was monitored by methods. Cremophors caused concentration- time-dependent damage both cells. Endothelial more sensitive surfactant treatment than cells, cell types. Our results support complement previously experimentally described may be related recognized side-effects medicines containing EL. Sucrose fatty acid esters increasingly investigated as research some them Pharmacopoeias European Union United States. Several studies documented properties toxicity profile, mode action efficacy models. Three water soluble sucrose esters, palmitate (P-1695), myristate (M-1695), laurate (D-1216), two reference enhancers, Tween 80 tested Caco-2 non-toxic significantly reduced resistance impedance not surfactants. All increased permeability for drugs fluidized plasma membrane, did visibly open tight junctions. inhibit P-glycoprotein. addition dissolution increasing can enhance through transcellular paracellular routes this is unrelated P-glycoprotein inhibition. The presented demonstrate differences between cellular actions various non-ionic excipients, important development new formulations delivery systems.