Abstract 2146: Echogenic Liposomes for Nitric Oxide Delivery
Introduction: Nitric oxide (NO) is a bioactive gas that is not sufficiently stable to be direct delivered to the vasculature.
Hypothesis: Echogenic liposomes, which encapsulate gases, can deliver nitric oxide to cells.
Methods: Phosphatidylcholine and cholesterol, pluspositively or negatively charged lipid, were used to prepare liposomes by a method involving hydrating the lipid film, sonication, and then freezing and thawing. Nitric oxide, alone or mixted with another gas, was was used to pressurize the lipid dispersion under 6 atm subsequent to sonication step. Cationic liposomes provided the highestnitric oxide incorporation and delivery to cells. Cell uptake was detected by specific fluorescent probe DFA-2DA. Cell cGMP activity was measured to evaluate the biologic effect of delivered NO.
Results: The procedure generates liposomes that contain 30 μl of NO in 5 mg lipids. Passive NO release was rapid for the first 30 min and slow for 8 hr thereafter. (The release rate can be adjusted by mixing NO with other encapsulated gases.) Delivery of nitric oxide into cultured cells by this means increased the production of intercellular cGMP. The potent nitric oxide scavenger, hemoglobin, did not affect nitric oxide activity.
Conclusion: NO encapsulation, release and preservation of activity in vascular smooth muscle cells–in the presence of a NO scavenger–has been demonstrated. This technique opens new possibilities for for the delivery of a variety of bioactive gases that would have little effect upon systemic administration without protection.