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 density lipoprotein (LDL) complex on experimental atherosclerosis in vivo, we examined whether DP-LDL complex could be effective for cholesterol ester accumulation in the aorta of atherogenic mice. Nonatherogenic and atherogenic mice were fed with normal and atherogenic diet for 14 weeks, respectively. Dexamethasone (DEX), lipid emulsion containing DP (DP-LE), or DP-LDL complex was intravenously injected once a week from 8 to 14 weeks. Cholesterol levels in serum and aorta in the atherogenic mice were significantly higher than those of nonatherogenic mice. Injection of DP-LDL complex significantly reduced cholesterol ester (CE) accumulation in the aorta of atherogenic mice. The reduction of CE accumulation in aorta treated with DP-LDL complexes was 10 and 100 times more potent than that with DP-LE and DEX, respectively. The radioactivity in the aorta of atherogenic mice treated with 3H-DP-LDL complex was significantly higher than that with 3H-DP-LE and 3H-DEX at 24 h after injection. Even 7 d after injection, a significant amount of radioactivity was present only in the aorta of atherogenic mice treated with DP-LDL complex. This result suggests that DP-LDL complex is selectively delivered 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 system for atherosclerosis.
Tauchi
Y
Y
Department of Pharmaceutics, Hokkaido College of Pharmacy, Otaru, Japan. y-tauchi@hokuyakudai.ac.jp
Zushida
L
L
Chono
S
S
Sato
J
J
Ito
K
K
Morimoto
K
K
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D001161:Arteriosclerosis / Q000378:metabolism* / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood / Q000378:metabolism*; D003907:Dexamethasone / Q000493:pharmacokinetics / Q000494:pharmacology*; D004036:Diet, Atherogenic; D005260:Female; D008099:Liver / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D010168:Palmitates / Q000493:pharmacokinetics / Q000494:pharmacology*
D002788:Cholesterol Esters; D010168:Palmitates; D003907:Dexamethasone; D002784:Cholesterol