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Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluids on alveolar surfaces

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Abstract

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.

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Acknowledgments

This work was supported in part by a Grant-in Aid (No. 25870654) for Young Scientists (B) provided by the Japan Society for the Promotion of Science (JSPS) and in part by a Grant-in Aid (2013) provided by the Akiyama Life Science Foundation (Sapporo, Japan).

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Authors and Affiliations

  1. Division of Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine, Sapporo, Hokkaido, 006-8590, Japan

    Keita Kaneko, Kohei Togami, Eri Yamamoto, Shujun Wang, Kazuhiro Morimoto & Sumio Chono

  2. Nihon Pharmaceutical University, Ina, Japan

    Kazuhiro Morimoto

  3. Department of Pharmacy, Hirosaki University School of Medicine and Hospital, 53, Hon-cho, Hirosaki, 036-8563, Japan

    Shirou Itagaki

Authors
  1. Keita Kaneko
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  2. Kohei Togami
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  3. Eri Yamamoto
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  4. Shujun Wang
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  5. Kazuhiro Morimoto
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  6. Shirou Itagaki
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  7. Sumio Chono
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Correspondence to Sumio Chono.

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The authors declare no conflicts of interest.

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Shujun Wang is on leave from Shenyang Pharmaceutical University, China.

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Kaneko, K., Togami, K., Yamamoto, E. et al. Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluids on alveolar surfaces. Drug Deliv. and Transl. Res. 6, 565–571 (2016). https://doi.org/10.1007/s13346-016-0310-2

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  • DOI: https://doi.org/10.1007/s13346-016-0310-2

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