Bone marrow-targeted liposomal carriers: a feasibility study in nonhuman primates.
OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
This finding increases the feasibility of using this bone marrow-specific drug-delivery system for clinical applications.
Sou
Keitaro
K
Center for Advanced Biomedical Sciences, Waseda University (TWIns), Tokyo 162-8480, Japan. so@kurenai.waseda.jp
Goins
Beth
B
Leland
Michelle M
MM
Tsuchida
Eishun
E
Phillips
William T
WT
D000818:Animals; D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics*; D008253:Macaca mulatta; D008297:Male; D011877:Radionuclide Imaging; D013667:Technetium
D008081:Liposomes; D013667:Technetium