2006 Fiscal Year Final Research Report Summary
Development of protein drug delivery system from the lung based on ligand recognition mechanisms of the receptors
| Project/Area Number |
17590125
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
TAKANO Mikihisa Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (20211336)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Junya Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (20301301)
YUMOTO Ryoko Hiroshima University, Center of Technology, Center Staff, 技術センター, 技術班長 (70379915)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Alveolar epithelial cells / Endocytosis / Albumin / Insulin / Clathrin / Caveolae / Receptor / Drug delivery system |
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| Research Abstract |
The purpose of this study is to obtain the information for the development of protein drug delivery system from the lung. I examined the uptake of FITC-1abeled albumin and insulin by alveolar type II epithelial cells using cultured RLE-6TN cells as well as primary cultured alveolar type II cells isolated from rats.
1. FITC-Albumin uptake by RLE-6TN cells was temperature-, concentration-, and energy-dependent. The uptake was mediated by high-affinity and low-affinity systems, and the former system was found to be the clathrin-mediated endocytosis.
2. The uptake of FITC-insulin by RLE-6TN cells was partly mediated by the clathrin-mediated endocytosis, but other systems would also be involved.
3. The fate of FITC-albumin and insulin taken up by RLE-6TN cells was examined. These proteins were partly localized in lysosomes, and gradually degraded over time.
4. Ligand blot analysis showed that there were some possible receptor proteins for albumin in the plasma membranes of RLE-6TN cells.
5. FITC-Albumin uptake by primary cultured alveolar type II cells isolated from rats was shown to be mediated by the clathrin-mediated endocytosis, like the uptake in RLE-6TN cells.
Further studies concerning the activities of protein drug uptake by alveolar type II and I cells, related receptors, the mechanisms of ligand recognition by the receptors would help to develop new strategies for protein drug delivery system from the lung.
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