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Aortic drug delivery of dexamethasone palmitate incorporated into lipid microspheres and its antiatherosclerotic effect in atherogenic mice

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°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°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.