Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluid on alveolus surface
Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluid on alveolus surface
复制标题
气雾化聚乙二醇化脂质体在肺泡表面上皮衬里液中的持续分布
DOI：
10.1007/s13346-016-0310-2
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Chono S
中科院分区：
文献类型：
--
作者：
Kaneko K;Togami K;Yamamoto E;Wang S;Morimoto K;Itagaki S;Chono S
研究了聚乙二醇化脂质体雾化在大鼠肺泡上皮内层液（ELF）中的分布特征，并通过体外吸收和蛋白吸附实验探讨了聚乙二醇化脂质体的作用机制。将未修饰或聚乙二醇化的脂质体（粒径100 nm）雾化到大鼠肺中。聚乙二醇化脂质体比未修饰的脂质体在内皮细胞中的分布更持久。此外，肺泡巨噬细胞（AMs）对聚乙二醇化脂质体的摄取少于未修饰的脂质体。在进一步的体外摄取实验中，未修饰的和聚乙二醇化的脂质体与大鼠ELF成分一起被调理，然后作为培养的大鼠AMs加入NR8383细胞中。NR8383细胞对调理化聚乙二醇脂质体的摄取低于调理化未修饰脂质体。此外，调理聚乙二醇脂质体的蛋白质吸收水平低于未修饰的脂质体。这些发现表明，雾化聚乙二醇化脂质体在elf中的持续分布反映了表面活性剂蛋白对脂质体的疏解，从而减少了AMs的摄取。这些数据表明，聚乙二醇化脂质体作为靶向ELF治疗呼吸系统疾病的气雾剂为基础的药物输送系统具有潜力。
The distribution characteristics of aerosolized PEGylated liposomes in alveolar epithelial lining fluid (ELF) were examined in rats, and the ensuing mechanisms were investigated in the in vitro uptake and protein adsorption experiments. Nonmodified or PEGylated liposomes (particle size 100 nm) were aerosolized into rat lungs. PEGylated liposomes were distributed more sustainably in ELFs than nonmodified liposomes. Furthermore, the uptake of PEGylated liposomes by alveolar macrophages (AMs) was less than that of nonmodified liposomes. In further in vitro uptake experiments, nonmodified and PEGylated liposomes were opsonized with rat ELF components and then added to NR8383 cells as cultured rat AMs. The uptake of opsonized PEGylated liposomes by NR8383 cells was lower than that of opsonized nonmodified liposomes. Moreover, the protein absorption levels in opsonized PEGylated liposomes were lower than those in opsonized nonmodified liposomes. These findings suggest that sustained distributions of aerosolized PEGylated liposomes in ELFs reflect evasion of liposomal opsonization with surfactant proteins and consequent reductions in uptake by AMs. These data indicate the potential of PEGylated liposomes as aerosol-based drug delivery system that target ELF for the treatment of respiratory diseases.