title: Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluids on alveolar surfaces.
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.
authors.affiliation: Division of Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine, Sapporo, Hokkaido, 006-8590, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Division of Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine, Sapporo, Hokkaido, 006-8590, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Togami
authors.affiliation: Division of Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine, Sapporo, Hokkaido, 006-8590, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Division of Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine, Sapporo, Hokkaido, 006-8590, Japan.
authors.forename: Shujun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Division of Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine, Sapporo, Hokkaido, 006-8590, Japan.|Nihon Pharmaceutical University, Ina, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Morimoto
authors.affiliation: Department of Pharmacy, Hirosaki University School of Medicine and Hospital, 53, Hon-cho, Hirosaki, 036-8563, Japan.
authors.forename: Shirou
authors.initials: S
authors.lastname: Itagaki
authors.affiliation: Division of Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine, Sapporo, Hokkaido, 006-8590, Japan. s-chono@hokuyakudai.ac.jp.
authors.forename: Sumio
authors.initials: S
authors.lastname: Chono
mesh_terms: D000336:Aerosols / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002478:Cells, Cultured; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D013499:Surface Properties
chemical_list: D000336:Aerosols; D008081:Liposomes; D011092:Polyethylene Glycols
keywords: Aerosol-based drug delivery system; Alveolar macrophages; Epithelial lining fluid; Opsonization; PEGylated liposomes