Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido Pharmaceutical University, Otaru, Japan.
Drug Dev Ind Pharm. 2010 Jan;36(1):102-7. doi: 10.3109/03639040903099744.
The effect of surface-mannose modification on aerosolized liposomal delivery to alveolar macrophages (AMs) was evaluated in vitro and in vivo.
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.
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.
These results indicate that surface-mannose modification is useful for efficient aerosolized liposomal delivery to AMs.
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。
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。
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。
这些结果表明，表面甘露糖修饰可用于高效的雾化脂质体向 AMs 的递药。
