title: Aortic drug delivery of dexamethasone palmitate incorporated into lipid microspheres and its antiatherosclerotic effect in atherogenic mice.
abstract: In order to confirm the efficacy of dexamethasone (DXM) palmitate incorporated into lipid microspheres (d-lipo) on atherosclerosis, the aortic drug delivery by d-lipo and its antiatherosclerotic effect were investigated. In an in vitro uptake experiment, d-lipo or DXM was added to macrophages and foam cells, and then incubated for 1, 4, 8 and 24 h at 37 degrees C. The uptake of drug by these cells after addition of d-lipo was higher than that of DXM at each time point. In an in vitro pharmacological experiment, the macrophages and foam cells were incubated with d-lipo or DXM for 24 h at 37 degrees C. The inhibitory effect of d-lipo on cellular cholesterol ester (CE) accumulation in these cells was significantly more potent than that of DXM. In an in vivo pharmacokinetic experiment, d-lipo or DXM was intravenously administered to atherogenic mice, and then aorta was collected at 1, 8, and 24 h after administration. The aortic drug concentration after administration of d-lipo to atherogenic mice was higher than that of DXM at each time point. In an in vivo pharmacological experiment, d-lipo or DXM was intravenously administered to atherogenic mice once a week for 7 weeks. The inhibitory effect of d-lipo on the aortic CE accumulation in atherogenic mice was significantly more potent than that of DXM. These findings suggest that efficient drug delivery to the atherosclerotic lesions by d-lipo produces an excellent antiatherosclerotic effect at a lower dose. Therefore, d-lipo may be useful for the development of drug delivery systems for atherosclerotic therapy.
authors.affiliation: Hokkaido Pharmaceutical University, Department of Pharmaceutics, 7-1 Katsuraoka-cho, Otaru-city 047-0264, Japan. s-chono@hokuyakudai.ac.jp
authors.forename: Sumio
authors.initials: S
authors.lastname: Chono
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tauchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000037:antagonists & inhibitors; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D005990:Glycerol; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008863:Microspheres; D010168:Palmitates / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010743:Phospholipids; D013024:Soybean Oil; D014018:Tissue Distribution
chemical_list: D000893:Anti-Inflammatory Agents; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D010168:Palmitates; D010743:Phospholipids; C099252:oxidized low density lipoprotein; D003907:Dexamethasone; D013024:Soybean Oil; D002784:Cholesterol; D005990:Glycerol