CORM-2-entrapped ultradeformable liposomes ameliorate acute skin inflammation in an ear edema model via effective CO delivery

The short release half-life of carbon monoxide(CO)is a major obstacle to the effective therapeutic use of carbon monoxide-releasing molecule-2(CORM-2).The potential of CORM-2-entrapped ultradeformable liposomes(CORM-2-UDLs)to enhance the release half-life of CO and alleviate skin inflammation was investigated in the present study.CORM-2-UDLs were prepared by using soy phosphatidylcholine to form lipid bilayers and Tween 80 as an edge activator.The deformability of CORM-2-UDLs was measured and compared with that of conventional liposomes by passing formulations through a filter device at a constant pressure.The release profile of CO from CORM-2-UDLs was evaluated by myoglobin assay.In vitro and in vivo anti-inflammatory effects of CORM-2-UDLs were assessed in lipopolysaccharide-stimulated macrophages and TPA-induced ear edema model,respectively.The deformability of the optimized CORM-2-UDLs was 2.3 times higher than conventional liposomes.CORM-2-UDLs significantly prolonged the release half-life of CO from 30 s in a CORM-2 solution to 21.6 min.CORM-2-UDLs demonstrated in vitro anti-inflammatory activity by decreasing nitrite production and pro-inflammatory cytokine levels.Furthermore,CORM-2-UDLs successfully ameliorated skin inflammation by reducing ear edema,pathological scores,neutrophil accumulation,and inflammatory cytokines expression.The results demonstrate that CORM-2-UDLs could be used as promising therapeutics against acute skin inflammation.