Liposomal delivery system of adenosine for modulating inflammation

Monocytes and neutrophils congregate at inflammatory tissues. We hypothesized that those cells can be exploited as transporters of liposomes (a particulate delivery system) to the inflammatory site for a potential therapeutic effect. The therapeutic application of adenosine, an endogenous purine nucleoside, is limited due to its very short circulating half-life. Several factors governing liposomal adenosine formulation have been studied. The optimal adenosine formulation in terms of stability and entrapment efficiency was the negatively charged liposomes (~200 nm), with a slow release profile of the drug. Liposomal adenosine exhibited preferential uptake by h-monocytes. No cytotoxic effect on rabbit SMC, h-neutrophils and monocytes, and murine macrophages in culture was found, and no depletion of circulating monocytes in rats. In addition, liposomal adenosine inhibited both TNFα and IL-6 activation in murine macrophages, and TNFα in h-monocytes. The liposomal adenosine formulation would appear suitable for evaluating its anti-inflammatory effect in animal models.