論文 - 詳細
| RRC ID | 63059 |
|---|---|
| 著者 | Togami K, Maruta Y, Nanbu M, Tada H, Chono S. |
| タイトル | Prolonged distribution of aerosolized PEGylated liposomes in the lungs of mice with bleomycin-induced pulmonary fibrosis. |
| ジャーナル | Drug Dev Ind Pharm |
| Abstract |
OBJECTIVE:Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic lung disease characterized by abnormal remodeling of the lung parenchyma with subsequent scarring of the alveolar structure. In this study, we examined the distribution characteristics of aerosolized polyethylene glycol (PEG)ylated liposomes in the lungs of mice with bleomycin-induced pulmonary fibrosis. SIGNIFICANCE:The present study details the utility of aerosolized PEGylated liposomes for improving intrapulmonary pharmacokinetics in fibrotic lungs. METHODS:Aerosolized PEGylated liposomes were administered to fibrotic mouse lungs using a MicroSprayer. Intrapulmonary pharmacokinetics was evaluated via in vivo imaging, measurement of liposome concentrations in bronchoalveolar lavage fluid (BALF) and alveolar macrophages (AMs), and observation of lung tissue sections. In addition, in vitro accumulation experiments using WI-38, A549, and RAW264.7 cells were performed. RESULTS:The decrease of the fluorescence intensity of the PEGylated liposomes was slower than that of the non-modified liposomes. Compared with the non-modified liposomes, the PEGylated liposomes were determined higher in BALF, whereas those in the AMs were lower. Both PEGylated and non-modified liposomes were widely dispersed in fibrotic regions in tissue sections. No difference in accumulation in WI-38 and A549 cells was noted between PEGylated and non-modified liposomes, whereas the PEGylated liposomes exhibited lower intracellular accumulation than non-modified liposomes in RAW264.7 cells. CONCLUSION:Aerosolized drug delivery systems using PEGylated liposomes exhibited prolonged distribution in both healthy and fibrotic mouse lungs. PEGylated liposomes were determined to be efficient drug delivery systems for anti-fibrotic agents targeting lung fibroblasts and alveolar epithelial cells for optimizing the treatment of IPF. |
| 巻・号 | 46(11) |
| ページ | 1873-1880 |
| 公開日 | 2020-11-1 |
| DOI | 10.1080/03639045.2020.1825473 |
| PMID | 32940095 |
| MeSH | Animals Bleomycin* Liposomes* Lung Macrophages, Alveolar / chemistry Mice Polyethylene Glycols / chemistry |
| IF | 2.365 |
| リソース情報 | |
| ヒト・動物細胞 | WI-38(RCB0702) A549(RCB0098) |