Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals
Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra-long-acting capsule that dissolves in the stomach and deploys a star-sh...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/128845 |
| _version_ | 1826192200460926976 |
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| author | Bellinger, Andrew Jafari, Mousa Grant, Tyler M Zhang, Shiyi Slater, Hannah C. Wenger, Edward A. Mo, Stacy H. Lee, Young-Ah Mazdiyasni, Hormoz Barman, Ross Kogan, Lawrence Cleveland, Cody Booth, Lucas Bensel, Taylor A Minahan Jr, Daniel J Hurowitz, Haley M. Tai, Tammy Daily, Johanna Nikolic, Boris Wood, Lowell Eckhoff, Philip A. Langer, Robert S Traverso, Carlo Giovanni |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Bellinger, Andrew Jafari, Mousa Grant, Tyler M Zhang, Shiyi Slater, Hannah C. Wenger, Edward A. Mo, Stacy H. Lee, Young-Ah Mazdiyasni, Hormoz Barman, Ross Kogan, Lawrence Cleveland, Cody Booth, Lucas Bensel, Taylor A Minahan Jr, Daniel J Hurowitz, Haley M. Tai, Tammy Daily, Johanna Nikolic, Boris Wood, Lowell Eckhoff, Philip A. Langer, Robert S Traverso, Carlo Giovanni |
| author_sort | Bellinger, Andrew |
| collection | MIT |
| description | Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra-long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine largeanimal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malariatransmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malariatransmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra-long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy. |
| first_indexed | 2024-09-23T09:07:46Z |
| format | Article |
| id | mit-1721.1/128845 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:07:46Z |
| publishDate | 2020 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1288452022-09-26T10:40:23Z Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals Bellinger, Andrew Jafari, Mousa Grant, Tyler M Zhang, Shiyi Slater, Hannah C. Wenger, Edward A. Mo, Stacy H. Lee, Young-Ah Mazdiyasni, Hormoz Barman, Ross Kogan, Lawrence Cleveland, Cody Booth, Lucas Bensel, Taylor A Minahan Jr, Daniel J Hurowitz, Haley M. Tai, Tammy Daily, Johanna Nikolic, Boris Wood, Lowell Eckhoff, Philip A. Langer, Robert S Traverso, Carlo Giovanni Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra-long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine largeanimal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malariatransmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malariatransmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra-long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy. NIH (Grants EB-000244 and T32-5T32HL007604-29), Bill and Melinda Gates Foundation (Grants OPP1096734, OPP1139921 and OPP1068440) 2020-12-16T17:04:46Z 2020-12-16T17:04:46Z 2016-11 2016-05 2019-08-22T17:09:37Z Article http://purl.org/eprint/type/JournalArticle 1946-6234 1946-6242 https://hdl.handle.net/1721.1/128845 Bellinger, Andrew M. et al. "Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals." 8, 365 (November 2016): 365ra157 © 2016 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. en http://dx.doi.org/10.1126/scitranslmed.aag2374 Science Translational Medicine Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Bellinger, Andrew Jafari, Mousa Grant, Tyler M Zhang, Shiyi Slater, Hannah C. Wenger, Edward A. Mo, Stacy H. Lee, Young-Ah Mazdiyasni, Hormoz Barman, Ross Kogan, Lawrence Cleveland, Cody Booth, Lucas Bensel, Taylor A Minahan Jr, Daniel J Hurowitz, Haley M. Tai, Tammy Daily, Johanna Nikolic, Boris Wood, Lowell Eckhoff, Philip A. Langer, Robert S Traverso, Carlo Giovanni Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals |
| title | Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals |
| title_full | Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals |
| title_fullStr | Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals |
| title_full_unstemmed | Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals |
| title_short | Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals |
| title_sort | oral ultra long lasting drug delivery application toward malaria elimination goals |
| url | https://hdl.handle.net/1721.1/128845 |
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