Design of Insulin-Loaded Nanoparticles Enabled by Multistep Control of Nanoprecipitation and Zinc Chelation
Nanoparticle (NP) carriers provide new opportunities for controlled delivery of drugs, and have potential to address challenges such as effective oral delivery of insulin. However, due to the difficulty of efficiently loading insulin and other proteins inside polymeric NPs, their use has been mostly...
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| Format: | Article |
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American Chemical Society (ACS)
2018
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| Online Access: | http://hdl.handle.net/1721.1/119690 https://orcid.org/0000-0003-1856-1925 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-0588-9286 |
| _version_ | 1826196023522885632 |
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| author | Chopra, Sunandini Bertrand, Nicolas Lim, Jong-Min Wang, Amy Farokhzad, Omid C Karnik, Rohit |
| author2 | Institute for Medical Engineering and Science |
| author_facet | Institute for Medical Engineering and Science Chopra, Sunandini Bertrand, Nicolas Lim, Jong-Min Wang, Amy Farokhzad, Omid C Karnik, Rohit |
| author_sort | Chopra, Sunandini |
| collection | MIT |
| description | Nanoparticle (NP) carriers provide new opportunities for controlled delivery of drugs, and have potential to address challenges such as effective oral delivery of insulin. However, due to the difficulty of efficiently loading insulin and other proteins inside polymeric NPs, their use has been mostly restricted to the encapsulation of small molecules. To better understand the processes involved in encapsulation of proteins in NPs, we study how buffer conditions, ionic chelation, and preparation methods influence insulin loading in poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) NPs. We report that, although insulin is weakly bound and easily released from the NPs in the presence of buffer ions, insulin loading can be increased by over 10-fold with the use of chelating zinc ions and by the optimization of the pH during nanoprecipitation. We further provide ways of changing synthesis parameters to control NP size while maintaining high insulin loading. These results provide a simple method to enhance insulin loading of PLGA-PEG NPs and provide insights that may extend to other protein drug delivery systems that are subject to limited loading. |
| first_indexed | 2024-09-23T10:19:36Z |
| format | Article |
| id | mit-1721.1/119690 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T10:19:36Z |
| publishDate | 2018 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1196902022-09-26T17:15:22Z Design of Insulin-Loaded Nanoparticles Enabled by Multistep Control of Nanoprecipitation and Zinc Chelation Chopra, Sunandini Bertrand, Nicolas Lim, Jong-Min Wang, Amy Farokhzad, Omid C Karnik, Rohit Institute for Medical Engineering and Science Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Chopra, Sunandini Bertrand, Nicolas Lim, Jong-Min Wang, Amy Farokhzad, Omid C Karnik, Rohit Nanoparticle (NP) carriers provide new opportunities for controlled delivery of drugs, and have potential to address challenges such as effective oral delivery of insulin. However, due to the difficulty of efficiently loading insulin and other proteins inside polymeric NPs, their use has been mostly restricted to the encapsulation of small molecules. To better understand the processes involved in encapsulation of proteins in NPs, we study how buffer conditions, ionic chelation, and preparation methods influence insulin loading in poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) NPs. We report that, although insulin is weakly bound and easily released from the NPs in the presence of buffer ions, insulin loading can be increased by over 10-fold with the use of chelating zinc ions and by the optimization of the pH during nanoprecipitation. We further provide ways of changing synthesis parameters to control NP size while maintaining high insulin loading. These results provide a simple method to enhance insulin loading of PLGA-PEG NPs and provide insights that may extend to other protein drug delivery systems that are subject to limited loading. National Science Foundation (U.S.) (award number DMR-0819762) Canadian Institutes of Health Research (postdoctoral fellowship) National Institutes of Health (U.S.) (Grant R01 EB015419) 2018-12-18T19:39:53Z 2018-12-18T19:39:53Z 2017-04 2018-12-06T15:31:07Z Article http://purl.org/eprint/type/JournalArticle 1944-8244 1944-8252 http://hdl.handle.net/1721.1/119690 Chopra, Sunandini, Nicolas Bertrand, Jong-Min Lim, Amy Wang, Omid C. Farokhzad, and Rohit Karnik. “Design of Insulin-Loaded Nanoparticles Enabled by Multistep Control of Nanoprecipitation and Zinc Chelation.” ACS Applied Materials & Interfaces 9, no. 13 (March 21, 2017): 11440–11450. https://orcid.org/0000-0003-1856-1925 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-0588-9286 http://dx.doi.org/10.1021/ACSAMI.6B16854 ACS Applied Materials & Interfaces Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Chopra, Sunandini Bertrand, Nicolas Lim, Jong-Min Wang, Amy Farokhzad, Omid C Karnik, Rohit Design of Insulin-Loaded Nanoparticles Enabled by Multistep Control of Nanoprecipitation and Zinc Chelation |
| title | Design of Insulin-Loaded Nanoparticles Enabled by Multistep Control of Nanoprecipitation and Zinc Chelation |
| title_full | Design of Insulin-Loaded Nanoparticles Enabled by Multistep Control of Nanoprecipitation and Zinc Chelation |
| title_fullStr | Design of Insulin-Loaded Nanoparticles Enabled by Multistep Control of Nanoprecipitation and Zinc Chelation |
| title_full_unstemmed | Design of Insulin-Loaded Nanoparticles Enabled by Multistep Control of Nanoprecipitation and Zinc Chelation |
| title_short | Design of Insulin-Loaded Nanoparticles Enabled by Multistep Control of Nanoprecipitation and Zinc Chelation |
| title_sort | design of insulin loaded nanoparticles enabled by multistep control of nanoprecipitation and zinc chelation |
| url | http://hdl.handle.net/1721.1/119690 https://orcid.org/0000-0003-1856-1925 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-0588-9286 |
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