Abstract 1431: Nitric Oxide Loaded Echogenic Liposomes Inhibit Intimal Hyperplasia in an Acute Arterial Injury Model
Introduction: Nitric oxide (NO) has potent biological activities but by itself is too labile for in vivo delivery to the vasculature. We have previously demonstrated that NO can be loaded into echogenic liposomes utilizing a freezing under pressure method and delivered into cells even in the presence of hemoglobin (a NO-scavenger).
Hypothesis: Nitric oxide loaded echogenic liposomes can deliver their contents into arterial wall causing vasodilatation and inhibit intimal hyperplasia in vivo.
Methods: Liposomes were prepared with a procedurce involving: lipid hydration, sonication, pressurization under Argon-NO(9:1 at 10 atm),freezing, pressure reduction to ambiant and thawing. For the model of acute arterial injury, rabbits were fed a high-fat diet for 2 weeks, followed by balloon injury to the common carotid artery. In the treatment group, NO-liposomes were administered intraarterially into the common carotid artery. Fourteen days later the carotid arteries were removed for histological examination of intimal thickening.
Results: This novel technique produces liposomes containing 30 μl of gaseous mixture of NO and argon in 5 mg of lipids. Acute administration of NO loaded liposomes to balloon-injured carotid arteries resulted in 51±6% inhibition of intimal thickening.
Conclusion: We have developed NO loaded liposomes with the capacity to release their payload in their active form and inhibit hyperplasia following acute injury. This technique provides a new way to load biologically labile bioactive gases into liposomes for in vivo administration.