Development of a corticosteroid incorporated in lipid microspheres (liposteroid).
Anti-inflammatory properties of liposteroid, a lipid emulsion containing dexamethasone palmitate in the particles, were investigated in comparison with those of water-soluble dexamethasone phosphate. In the acute inflammatory model of carrageenin oedema in rats, liposteroid was as effective as dexamethasone phosphate, whereas liposteroid was twice as effective on formalin granuloma, 3.3 times on adjuvant arthritis and 5.3 times on carrageenin granuloma in rats. Distribution of dexamethasone to the inflammatory lesion in rats with adjuvant arthritis was markedly higher in the liposteroid group than in the dexamethasone phosphate group: 1.5 times higher in 2-6 hours and approximately twice in 24 h. The uptake rate of steroid by rat peritoneal macrophages was greater with liposteroid than with dexamethasone phosphate. Furthermore, the inhibitory effects of liposteroid on Fc receptor dependent phagocytosis activity, superoxide anion release and chemotaxis of the macrophages were more potent than those of dexamethasone phosphate. Dexamethasone palmitate itself had very weak activity compared with dexamethasone in the blanching phenomena test in volunteers and dexamethasone palmitate in liposteroid was hydrolysed to dexamethasone in human monocytes. This study suggests that corticosteroids incorporated in lipid emulsions are taken up by the macrophages to a much greater extent than free corticosteroids and strongly suppress macrophage functions, resulting in stronger anti-inflammatory activity.
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006099:Granuloma / Q000139:chemically induced / Q000188:drug therapy; D008081:Liposomes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D004337:Drug Carriers; D008081:Liposomes; C035081:dexamethasone 21-palmitate; D003907:Dexamethasone