The objective of this study was to determine the cellular uptake of stavudine (an approved drug for AIDS treatment) by human monocyte/macrophages (U 937). The effect of lipid used, cholesterol concentration and the presence of charge on the liposome bilayer, on the cellular uptake by monocyte/macrophages was investigated. Liposomes employed in the study were prepared by reverse phase evaporation. The lipids egg PC, DMPC, DPPC, DSPC, DMPG and sphingomyelin were employed in this study. The effect of cholesterol on cellular uptake was studied by using liposomes containing a constant amount of lipid and varying amounts of cholesterol. Stearylamine or dicetylphosphate (10 mol%) was used to induce positive or negative charge on the bilayer. The cells were separated from liposomes by centrifugation in membrane filters and the amount of stavudine taken up by macrophages was estimated using tritium labeled drug as a marker. Stavudine uptake was found to be the maximum (approximately 950 ng/million cells) in liposomes containing dipalmitoyl phosphatidylcholine (DPPC). The presence of sphingomyelin, which increases bilayer rigidity decreased cellular uptake of stavudine and the presence of negative charge on the bilayer, enhanced the uptake of stavudine compared to positive charge. There is no apparent difference in uptake when varying amounts of cholesterol was added to liposomal formulations. The present study shows that the sensitivity of macrophages to different charge and lipid type can be used to either decrease or increase cellular uptake as desired.
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