Factors influencing polycation/siRNA colloidal stability toward aerosol lung delivery
Hexanediol diacrylate cross-linked oligoethylenimine (OEI-HD) is a non-viral polymeric vector designed to deliver siRNA. To achieve safe and effective in vivo siRNA delivery using this vector, the polyplex must have sufficient colloidal stability if administered intravenously or nebulized for delive...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2013
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| Online Access: | https://hdl.handle.net/10356/99404 http://hdl.handle.net/10220/16219 |
| _version_ | 1826121913841221632 |
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| author | Steele, Terry W. J. Zhao, Xiaobin Tarcha, Peter Kissel, Thomas |
| author2 | School of Materials Science & Engineering |
| author_facet | School of Materials Science & Engineering Steele, Terry W. J. Zhao, Xiaobin Tarcha, Peter Kissel, Thomas |
| author_sort | Steele, Terry W. J. |
| collection | NTU |
| description | Hexanediol diacrylate cross-linked oligoethylenimine (OEI-HD) is a non-viral polymeric vector designed to deliver siRNA. To achieve safe and effective in vivo siRNA delivery using this vector, the polyplex must have sufficient colloidal stability if administered intravenously or nebulized for delivery by the pulmonary route. In this study, polyplexes from OEI-HD and siRNA were formulated for aerosol-based lung delivery, regarding their colloidal stability, optimal particle size, and in vitro biological activity. Herein, we describe how these properties are dependent upon the polymer-to siRNA weight ratios, buffer composition they were complexed in, PEG-grafting, and the addition of commercial lung surfactants and/or non-ionic surfactants to the formulation. Lastly, the effects of nebulization of the formulation into aerosol droplets, on the polyplex particle size and transfection efficiency, were evaluated.
Polyplex size was monitored for up to 2 h after polyplex formation to determine the extent of aggregation and final particle sizes when stability was achieved. Our results suggest that PEG-grafting and polyethylenimine-PEG mixing were effective in achieving colloidal stability in isotonic saline buffers. In addition, colloidal stability was achieved in isotonic glucose buffers using commercially available non-ionic surfactant Pluronic™ P68 or the lung-derived surfactant Alveofact™. The smallest particle size, 140 nm, was obtained with Pluronic™ F68. For transfection efficiency, both Alveofact™ and Pluronic™ F68 achieved equal or better transfection when added to the OEI-HD/siRNA polyplexes. For long term storage of OEI-HD/siRNA formulations, we propose a lyophilization method that created in situ polyplexes upon addition of water. Preparation of OEI-HD/siRNA polyplexes by this method allowed dry storage at room temperature for up to the 3 months. In conclusion, we have identified approaches to achieve formulation and colloidal stability of OEI-HD/siRNA complexes, a step toward successful application of polyplexes for in vivo siRNA delivery. |
| first_indexed | 2024-10-01T05:39:56Z |
| format | Journal Article |
| id | ntu-10356/99404 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:39:56Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/994042020-06-01T10:13:35Z Factors influencing polycation/siRNA colloidal stability toward aerosol lung delivery Steele, Terry W. J. Zhao, Xiaobin Tarcha, Peter Kissel, Thomas School of Materials Science & Engineering DRNTU::Engineering::Materials Hexanediol diacrylate cross-linked oligoethylenimine (OEI-HD) is a non-viral polymeric vector designed to deliver siRNA. To achieve safe and effective in vivo siRNA delivery using this vector, the polyplex must have sufficient colloidal stability if administered intravenously or nebulized for delivery by the pulmonary route. In this study, polyplexes from OEI-HD and siRNA were formulated for aerosol-based lung delivery, regarding their colloidal stability, optimal particle size, and in vitro biological activity. Herein, we describe how these properties are dependent upon the polymer-to siRNA weight ratios, buffer composition they were complexed in, PEG-grafting, and the addition of commercial lung surfactants and/or non-ionic surfactants to the formulation. Lastly, the effects of nebulization of the formulation into aerosol droplets, on the polyplex particle size and transfection efficiency, were evaluated. Polyplex size was monitored for up to 2 h after polyplex formation to determine the extent of aggregation and final particle sizes when stability was achieved. Our results suggest that PEG-grafting and polyethylenimine-PEG mixing were effective in achieving colloidal stability in isotonic saline buffers. In addition, colloidal stability was achieved in isotonic glucose buffers using commercially available non-ionic surfactant Pluronic™ P68 or the lung-derived surfactant Alveofact™. The smallest particle size, 140 nm, was obtained with Pluronic™ F68. For transfection efficiency, both Alveofact™ and Pluronic™ F68 achieved equal or better transfection when added to the OEI-HD/siRNA polyplexes. For long term storage of OEI-HD/siRNA formulations, we propose a lyophilization method that created in situ polyplexes upon addition of water. Preparation of OEI-HD/siRNA polyplexes by this method allowed dry storage at room temperature for up to the 3 months. In conclusion, we have identified approaches to achieve formulation and colloidal stability of OEI-HD/siRNA complexes, a step toward successful application of polyplexes for in vivo siRNA delivery. 2013-10-03T01:53:06Z 2019-12-06T20:06:50Z 2013-10-03T01:53:06Z 2019-12-06T20:06:50Z 2011 2011 Journal Article Steele, T. W. J., Zhao, X., Tarcha, P., & Kissel, T. (2011). Factors influencing polycation/siRNA colloidal stability toward aerosol lung delivery. European journal of pharmaceutics and biopharmaceutics, 80(1), 14-24. https://hdl.handle.net/10356/99404 http://hdl.handle.net/10220/16219 10.1016/j.ejpb.2011.08.008 en European journal of pharmaceutics and biopharmaceutics |
| spellingShingle | DRNTU::Engineering::Materials Steele, Terry W. J. Zhao, Xiaobin Tarcha, Peter Kissel, Thomas Factors influencing polycation/siRNA colloidal stability toward aerosol lung delivery |
| title | Factors influencing polycation/siRNA colloidal stability toward aerosol lung delivery |
| title_full | Factors influencing polycation/siRNA colloidal stability toward aerosol lung delivery |
| title_fullStr | Factors influencing polycation/siRNA colloidal stability toward aerosol lung delivery |
| title_full_unstemmed | Factors influencing polycation/siRNA colloidal stability toward aerosol lung delivery |
| title_short | Factors influencing polycation/siRNA colloidal stability toward aerosol lung delivery |
| title_sort | factors influencing polycation sirna colloidal stability toward aerosol lung delivery |
| topic | DRNTU::Engineering::Materials |
| url | https://hdl.handle.net/10356/99404 http://hdl.handle.net/10220/16219 |
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