Uptake of dexamethasone incorporated into liposomes by macrophages and foam cells and its inhibitory effect on cellular cholesterol ester accumulation

To confirm the efficacy of dexamethasone incorporated into liposomes in the treatment of atherosclerosis, the uptake of dexamethasone‐liposomes by macrophages and foam cells and its inhibitory effect on cellular cholesterol ester accumulation in these cells were investigated in‐vitro. Dexamethasone‐liposomes were prepared with egg yolk phosphatidylcholine, cholesterol and dicetylphosphate in a lipid molar ratio of 7/2/1 by the hydration method. This was adjusted to three different particle sizes to clarify the influence of particle size on the uptake by the macrophages and foam cells, and the inhibitory effect on cellular cholesterol ester accumulation. The distribution of particle sizes of dexamethasone‐liposomes were 518.7 ± 49.5nm (L500), 202.2± 23.1 nm (L200), and 68.6 ± 6.5 nm (L70), respectively. For each size, dexamethasone concentration and dexamethasone/lipid molar ratio in dexamethasone‐liposome suspension were 1 mg dexamethasone mL −1 and 0.134 mol dexamethasone mol −1 total lipids, respectively. The zeta potential was approximately −70 mV for all sizes. Dexamethasone‐liposomes or free dexamethasone were added to the macrophages in the presence of oxidized low density lipoprotein (oxLDL) and foam cells, and then incubated at 37°C. The uptake amount of dexamethasone by the macrophages and foam cells after a 24‐h incubation was L500 > L200 > free dexamethasone > L70. The macrophages in the presence of oxLDL and foam cells were incubated with dexamethasone‐liposomes or free dexamethasone for 24 h at 37°C to evaluate the inhibitory effect on the cellular cholesterol ester accumulation. The cellular cholesterol ester level in the macrophages treated with oxLDL was significantly increased compared with that in macrophages without additives. L500, L200 and free dexamethasone significantly inhibited this cholesterol ester accumulation. L500, L200 and free dexamethasone also significantly reduced cellular cholesterol ester accumulation in foam cells. In addition, the relationship between the area under the uptake amount of dexamethasone‐time curve (AUC) and the inhibition rate of cholesterol ester accumulation in macrophages and foam cells was evaluated. The inhibition rate of cholesterol ester accumulation (%) was related to the AUC in both types of cell. These results suggested that dexamethasone‐liposomes would be a useful approach to the development of a novel drug delivery system for atherosclerotic therapy. Furthermore, the prediction of the inhibitory effect of dexamethasone on cellular cholesterol ester accumulation may become possible by using the results of this study.