Cellular uptake and elimination of lipophilic drug delivered by nanocarriers

To investigate the cellular uptake and elimination process of a lipophilic drug loaded in different nanocarriers, emulsions, liposomes and poly (DL-lactide-co-glycolide) (PLGA) nanoparticles loaded with a model drug, coumarin 6, were prepared and their transportation in HeLa cells compared. After 4 h incubation, liposomes and nanoparticles mediated significantly higher intracellular drug levels, which were 3 or 2.5 times that of the emulsion group, into cells. A novel kinetic model was established to analyze the cellular elimination process. Emulsions had the longest intracellular mean residence time (MRT), which was about 1-2 times longer than other nanocarriers. The endocytosis inhibition experiment suggested that the coumarin 6 in liposomes and nanoparticles entered cells directly via diffusion, while part of the intracellular coumarin 6 was taken up through clathrin-mediated endocytosis in emulsions. Combined with the results on uptake pathway and kinetic parameters, it can be concluded that different nanocarriers bring about diverse mechanisms of cellular uptake and elimination.