Effect of surface-mannose modification on aerosolized liposomal delivery to alveolar macrophages.
OBJECTIVE
The effect of surface-mannose modification on aerosolized liposomal delivery to alveolar macrophages (AMs) was evaluated in vitro and in vivo.


METHODS
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.


CONCLUSIONS
These results indicate that surface-mannose modification is useful for efficient aerosolized liposomal delivery to AMs.
Chono
Sumio
S
Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido Pharmaceutical University, Otaru, Japan. s-chono@hokuyakudai.ac.jp
Kaneko
Keita
K
Yamamoto
Eri
E
Togami
Kohei
K
Morimoto
Kazuhiro
K
D000336:Aerosols; D000814:Aniline Compounds / Q000737:chemistry*; D000818:Animals; D016503:Drug Delivery Systems; D008081:Liposomes; D008168:Lung / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008362:Mannosides / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
D000336:Aerosols; D000814:Aniline Compounds; D008081:Liposomes; D008362:Mannosides; C034056:4-aminophenylmannoside