Elucidation of intestinal absorption mechanism of carvedilol-loaded solid lipid nanoparticles using Caco-2 cell line as an in-vitro model

Abstract

Enhanced oral bioavailability of poorly aqueous soluble drugs encapsulated in solid lipid nanoparticles (SLNs) via lymphatic delivery has been documented. Since no in-vitro lymphoid tissue is currently available, human excised Caco-2 cell monolayer could be alternative tissue for development of an in-vitro model to be used as a screening tool before animal studies are undertaken. Therefore, optimized carvedilol-loaded SLNs (FOPT-SLNs) were prepared, characterized, and evaluated using Caco-2 cell line as an in-vitro model. Physical mixture of components of FOPT-SLNs (FOPT-PM) and carvedilol solution were used as control groups. From the studies of effect of SLNs concentration and cells incubation time, suitable carvedilol concentration and incubation time were selected for the model in which cells were subjected to five pretreatments for 24 h or 1 h of cell incubation and then followed with treatment of FOPT-SLNs, FOPT-PM or 100 µg/mL solution of carvedilol, for additional 24 h of cell incubation. The results obtained in this model suggest that main absorption mechanism of FOPT-SLNs could be endocytosis and, more specifically, clathrin-mediated endocytosis. When Transwell® permeable supports were used for the cells, carrier-mediated mechanism for FOPT-SLNs and passive absorption mechanism (transcellular and paracellular) for FOPT-PM and drug solution were concluded.