Abstract

Recently, we described a novel surface-modified lipid vesicle formulation (liposome) that had very high targeting to bone marrow in normal rabbits. Because the bone marrow is the site of hematopoiesis, bone marrow-targeted drug-delivery systems have many potential applications. In this study we investigated whether these bone marrow-targeted vesicles are also similarly effective for bone marrow targeting in rhesus monkeys, a primate animal model that is more relevant to humans. The preformed vesicles encapsulating 30 mM glutathione were labeled with technetium-99m ((99m)Tc) for scintigraphic imaging. The vesicles were 216 +/- 21 nm in diameter with a negative surface charge composed of DPPC, cholesterol, anionic amphiphile and poly(ethylene glycol)-DSPE (1:1:0.2:0.013 molar ratio). The whole-body images of rhesus monkeys receiving intravenous (99m)Tc vesicles revealed high uptake of the (99m)Tc vesicles in bone marrow. Based on image analysis, we estimated that approximately 70% of the injected dose of the (99m)Tc vesicles was taken up by the bone marrow. This finding increases the feasibility of using this bone marrow-specific drug-delivery system for clinical applications.

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