Bone Marrow-Targeted Liposomal Carriers: A Feasibility Study in Nonhuman Primates

Abstract

Background & aims: 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. Materials & methods: The preformed vesicles encapsulating 30 mM glutathione were labeled with technetium-99m (^99mTc) 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 ^99mTc vesicles revealed high uptake of the ^99mTc vesicles in bone marrow. Based on image analysis, we estimated that approximately 70% of the injected dose of the ^99mTc vesicles was taken up by the bone marrow. Conclusion: This finding increases the feasibility of using this bone marrow-specific drug-delivery system for clinical applications.

Keywords::

• biodistribution
• bone marrow
• drug carrier
• lipid vesicles
• liposomes
• nonhuman primate
• scintigraphy
• surface modification

Financial & competing interests disclosure

This work was partly supported by the Japan Society for the Promotion of Science (JSPS) Bilateral Joint Project between Japan-US. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was partly supported by the Japan Society for the Promotion of Science (JSPS) Bilateral Joint Project between Japan-US. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.