Inhibition of human neutrophil elastase by α 1-antitrypsin functionalized colloidal microcarriers
Layer-by-layer (LbL)-coated microcarriers offer a good opportunity as transport systems for active agents into specific cells and tissues. The assembling of oppositely charged polyelectrolytes enables a modular construction of the carriers and therefore an optimized integration and application of dr...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2013
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| Online Access: | https://hdl.handle.net/10356/96480 http://hdl.handle.net/10220/10339 |
| _version_ | 1811678109471080448 |
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| author | Reibetanz, Uta Schönberg, Maria Rathmann, Sophie Strehlow, Vincent Göse, Martin Leßig, Jacqueline |
| author2 | School of Materials Science & Engineering |
| author_facet | School of Materials Science & Engineering Reibetanz, Uta Schönberg, Maria Rathmann, Sophie Strehlow, Vincent Göse, Martin Leßig, Jacqueline |
| author_sort | Reibetanz, Uta |
| collection | NTU |
| description | Layer-by-layer (LbL)-coated microcarriers offer a good opportunity as transport systems for active agents into specific cells and tissues. The assembling of oppositely charged polyelectrolytes enables a modular construction of the carriers and therefore an optimized integration and application of drug molecules. Here, we report the multilayer incorporation and transport of α1-antitrypsin (AT) by colloidal microcarriers. AT is an anti-inflammatory agent and shows inhibitory effects toward its pro-inflammatory antagonist, human neutrophil elastase (HNE). The highly proteolytic enzyme HNE is released by polymorphonuclear leukocytes (PMNs) during inflammatory processes and can cause host tissue destruction and pain. The high potential of this study is based on a simultaneous intra- and extracellular application of AT-functionalized LbL carriers. Carrier application in PMNs results in significant HNE inhibition within 21 h. Microcarriers phagocytosed by PMNs were time dependently decomposed inside phagolysosomes, which enables the step-by-step release of AT. Here, AT inactivates HNE before being released, which avoids a further HNE concentration increase in the extracellular space and, subsequently, reduces the risk of further tissue destruction. Additionally, AT surface-functionalized microcarriers allow the inhibition of already released HNE in the extracellular space. Finally, this study demonstrates the successful application of LbL carriers for a concurrent extra- and intracellular HNE inhibition aiming the rebalancing of protease and antiprotease concentrations and the subsequent termination of chronic inflammations. |
| first_indexed | 2024-10-01T02:48:02Z |
| format | Journal Article |
| id | ntu-10356/96480 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:48:02Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/964802020-06-01T10:13:47Z Inhibition of human neutrophil elastase by α 1-antitrypsin functionalized colloidal microcarriers Reibetanz, Uta Schönberg, Maria Rathmann, Sophie Strehlow, Vincent Göse, Martin Leßig, Jacqueline School of Materials Science & Engineering Layer-by-layer (LbL)-coated microcarriers offer a good opportunity as transport systems for active agents into specific cells and tissues. The assembling of oppositely charged polyelectrolytes enables a modular construction of the carriers and therefore an optimized integration and application of drug molecules. Here, we report the multilayer incorporation and transport of α1-antitrypsin (AT) by colloidal microcarriers. AT is an anti-inflammatory agent and shows inhibitory effects toward its pro-inflammatory antagonist, human neutrophil elastase (HNE). The highly proteolytic enzyme HNE is released by polymorphonuclear leukocytes (PMNs) during inflammatory processes and can cause host tissue destruction and pain. The high potential of this study is based on a simultaneous intra- and extracellular application of AT-functionalized LbL carriers. Carrier application in PMNs results in significant HNE inhibition within 21 h. Microcarriers phagocytosed by PMNs were time dependently decomposed inside phagolysosomes, which enables the step-by-step release of AT. Here, AT inactivates HNE before being released, which avoids a further HNE concentration increase in the extracellular space and, subsequently, reduces the risk of further tissue destruction. Additionally, AT surface-functionalized microcarriers allow the inhibition of already released HNE in the extracellular space. Finally, this study demonstrates the successful application of LbL carriers for a concurrent extra- and intracellular HNE inhibition aiming the rebalancing of protease and antiprotease concentrations and the subsequent termination of chronic inflammations. 2013-06-13T06:21:27Z 2019-12-06T19:31:18Z 2013-06-13T06:21:27Z 2019-12-06T19:31:18Z 2012 2012 Journal Article Reibetanz, U., Schönberg, M., Rathmann, S., Strehlow, V., Göse, M., & Leßig, J. (2012). Inhibition of Human Neutrophil Elastase by α 1-Antitrypsin Functionalized Colloidal Microcarriers. ACS Nano, 6(7), 6325-6336. 1936-0851 https://hdl.handle.net/10356/96480 http://hdl.handle.net/10220/10339 10.1021/nn301791w en ACS nano © 2012 American Chemical Society. |
| spellingShingle | Reibetanz, Uta Schönberg, Maria Rathmann, Sophie Strehlow, Vincent Göse, Martin Leßig, Jacqueline Inhibition of human neutrophil elastase by α 1-antitrypsin functionalized colloidal microcarriers |
| title | Inhibition of human neutrophil elastase by α 1-antitrypsin functionalized colloidal microcarriers |
| title_full | Inhibition of human neutrophil elastase by α 1-antitrypsin functionalized colloidal microcarriers |
| title_fullStr | Inhibition of human neutrophil elastase by α 1-antitrypsin functionalized colloidal microcarriers |
| title_full_unstemmed | Inhibition of human neutrophil elastase by α 1-antitrypsin functionalized colloidal microcarriers |
| title_short | Inhibition of human neutrophil elastase by α 1-antitrypsin functionalized colloidal microcarriers |
| title_sort | inhibition of human neutrophil elastase by α 1 antitrypsin functionalized colloidal microcarriers |
| url | https://hdl.handle.net/10356/96480 http://hdl.handle.net/10220/10339 |
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