Abstract 5552: Bioactive Gas/Drug Co-encapsulation and Release Improve Attenuation of Intimal Hyperplasmia Following Acute Arterial Injury
Introduction: Evidence suggests that vascular smooth muscle cell proliferation, clot formation and inflammation play important roles in early vascular injury following intervention. A strategy with pleiotropic actions is more likely to be effective in limiting neointimal proliferation. Echogenic liposomes (ELIP) have the ability to encapsulate both bioactive gases (nitric oxide -NO) and pharmaceutics allowing attenuation of intimal hyperplasia following vascular injury.
Methods: Cationic liposomes containing nitric oxide (NO) and rosiglitazone were prepared by hydration, sonication and freeze-thawing. Pressurization of the lipid dispersion with NO/argon after sonication permits co-encapsulation of NO into the rosiglitazone-loaded ELIP. Acute arterial injury was created in rabbits using balloon injury to the common carotid artery. NO and rosiglitazone loaded ELIP were administered intraarterially into the common carotid artery. Fourteen days later the carotid arteries were removed for histologic examination.
Results: The technique resulted in 100 μg rosiglitazone and 10 μl NO/argon co-encapsulated into 1 mg of liposomes. The liposomes were rendered echogenic allowing ultrasound imaging of ELIP delivery and distribution. The combined NO-rosiglitazone delivery provided greater attenuation of intimal proliferation when compared to NO or rosiglitazone delivery alone (88±15% vs. 75±13% or 51±6%).
Conclusion: This novel methodology has the ability to direct two quite different agents to limit neointimal proliferation at the time acute intervention.