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  • 标题:Efficient Delivery to Human Lung Fibroblasts (WI-38) of Pirfenidone Incorporated into Liposomes Modified with Truncated Basic Fibroblast Growth Factor and Its Inhibitory Effect on Collagen Synthesis in Idiopathic Pulmonary Fibrosis
  • 本地全文:下载
  • 作者:Kohei Togami ; Aki Miyao ; Kei Miyakoshi
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2015
  • 卷号:38
  • 期号:2
  • 页码:270-276
  • DOI:10.1248/bpb.b14-00659
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    In the present in vitro study, we assessed the delivery of pirfenidone incorporated into liposomes modified with truncated basic fibroblast growth factor (tbFGF) to lung fibroblasts and investigated the anti-fibrotic effect of the drug. The tbFGF peptide, KRTGQYKLC, was used to modify the surface of liposomes (tbFGF-liposomes). We used the thin-layer evaporation method, followed by sonication, to prepare tbFGF-liposomes containing pirfenidone. The cellular accumulation of tbFGF-liposomes was 1.7-fold greater than that of non-modified liposomes in WI-38 cells used as a model of lung fibroblasts. Confocal laser scanning microscopy showed that tbFGF-liposomes were widely localized in WI-38 cells. The inhibitory effects of pirfenidone incorporated into tbFGF-liposomes on transforming growth factor-β1 (TGF-β1)-induced collagen synthesis in WI-38 cells were evaluated by measuring the level of intracellular hydroxyproline, a major component of the protein collagen. Pirfenidone incorporated into tbFGF-liposomes at concentrations of 10, 30, and 100 µM significantly decreased the TGF-β1-induced hydroxyproline content in WI-38 cells. The anti-fibrotic effect of pirfenidone incorporated into tbFGF-liposomes was enhanced compared with that of pirfenidone solution. These results indicate that tbFGF-liposomes are a useful drug delivery system of anti-fibrotic drugs to lung fibroblasts for the treatment of idiopathic pulmonary fibrosis.

  • 关键词:liposome; lung fibroblast (WI-38); truncated basic fibroblast growth factor; idiopathic pulmonary fibrosis; pirfenidone
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