表面甘露糖修饰对肺泡巨噬细胞吸入性脂质体递药的影响。

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

机构信息

Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido Pharmaceutical University, Otaru, Japan.

出版信息

Drug Dev Ind Pharm. 2010 Jan;36(1):102-7. doi: 10.3109/03639040903099744.

DOI:10.3109/03639040903099744

PMID:19656002

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.

摘要

目的

评估表面甘露糖修饰对肺泡巨噬细胞（AMs）吸入性脂质体递药的体内外效果。

方法

使用 4-氨基苯-α-D-甘露吡喃糖苷（Man）进行表面甘露糖修饰，并制备了具有不同甘露糖修饰率（粒径：1000nm）的甘露糖化脂质体。

结果

在体外摄取实验中，甘露糖化脂质体被 AMs 的摄取随着甘露糖修饰率在 2.4-9.1mol%Man 范围内的增加而增加，并在超过 9.1%Man 时保持恒定。因此，最有效的甘露糖修饰率为 9.1mol%Man。此外，游离甘露糖抑制 AMs 对甘露糖化脂质体的摄取。这表明 AMs 摄取甘露糖化脂质体的机制是甘露糖受体介导的内吞作用。在体内动物实验中，与未修饰的脂质体相比，经肺部雾化后，甘露糖化脂质体（甘露糖修饰率为 9.1mol%Man）更有效地递送至 AMs，且不损害肺组织。