Effect of dexamethasone palmitate-low density lipoprotein complex on cholesterol ester accumulation in aorta of atherogenic model mice

In order to confirm the efficacy of dexamethasone palmitate (DP)-low densit y lipoprotein (LDL) complex on experimental atherosclerosis in vivo, we exa mined whether DP-LDL complex could be effective for cholesterol ester accum ulation in the aorta of atherogenic mice. Nonatherogenic and atherogenic mi ce were fed with normal and atherogenic diet for 14 weeks, respectively. De xamethasone (DEX), lipid emulsion containing DP (DP-LE), or DP-LDL complex was intravenously injected once a week from 8 to 14 weeks. Cholesterol leve ls in serum and aorta in the atherogenic mice were significantly higher tha n those of nonatherogenic mice. Injection of DP-LDL complex significantly r educed cholesterol ester (CE) accumulation in the aorta of atherogenic mice . The reduction of CE accumulation in aorta treated with DP-LDL complexes w as 10 and 100 times more potent than that with DP-LE and DEX, respectively. The radioactivity in the aorta of atherogenic mice treated With H-3-DP-LDL complex was significantly higher than that with H-3-DP-LE and H-3-DEX at 2 4 h after injection. Even 7 d after injection, a significant amount of radi oactivity was present only in the aorta of atherogenic mice treated with DP -LDL complex. This result suggests that DP-LDL complex is selectively deliv ered to the atherogenic lesions in the aorta of atherogenic mice, and then DP released from the complex inhibits CE accumulation in the aortic intima. Therefore, DP-LDL complex may be a good drug-carrier in drug delivery syst em for atherosclerosis.