Effect of surface-mannose modification on aerosolized liposomal delivery to alveolar macrophages

Abstract

Purpose: The effect of surface-mannose modification on aerosolized liposomal delivery to alveolar macrophages (AMs) was evaluated in vitro and in vivo. Method: 4-Aminophenyl-α-D-mannopyranoside (Man) was used for surface-mannose modification, and mannosylated liposomes with various mannosylation rates (particle size: 1000 nm) were prepared. Results: In the in vitro uptake experiments, the uptake of mannosylated liposomes by AMs was increased with the increase in the mannosylation rate over the range 2.4–9.1 mol% Man and became constant at over 9.1%. Thus, the most efficient mannosylation rate was 9.1 mol% Man. Furthermore, free mannose inhibited the uptake of mannosylated liposomes by AMs. This indicates that the uptake mechanism of mannosylated liposomes by AMs is mannose receptor-mediated endocytosis. In the in vivo animal experiments, the mannosylated liposomes (mannosylation rate, 9.1 mol% Man) were more efficiently delivered to AMs after pulmonary aerosolization to rats than nonmodified liposomes and did not harm lung tissues. Conclusion: These results indicate that surface-mannose modification is useful for efficient aerosolized liposomal delivery to AMs.

Keywords:

• Alveolar macrophages
• liposomes
• NR8383 cells
• pulmonary aerosolization
• surface mannose modification

Acknowledgment

This work was supported in part by a Grant-in Aid (No. 20590039) for Scientific Research provided by Japan Society for the Promotion of Science.

Declaration of interest

The authors report no conflicts of interest.