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A robotic pill for oral delivery of biotherapeutics: safety, tolerability, and performance in healthy subjects
Biotherapeutics are highly efficacious, but the pain and inconvenience of chronic injections lead to poor patient compliance and compromise effective disease management. Despite innumerable attempts, oral delivery of biotherapeutics remains unsuccessful due to their degradation in the gastrointestin...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677648/ https://www.ncbi.nlm.nih.gov/pubmed/33604838 http://dx.doi.org/10.1007/s13346-021-00938-1 |
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author | Dhalla, Arvinder K. Al-Shamsie, Ziad Beraki, Simret Dasari, Anvesh Fung, Leonard C. Fusaro, Laura Garapaty, Anusha Gutierrez, Betsy Gratta, Delia Hashim, Mir Horlen, Kyle Karamchedu, Padma Korupolu, Radhika Liang, Eric Ong, Chang Owyang, Zachary Salgotra, Vasudha Sharma, Shilpy Syed, Baber Syed, Mansoor Vo, April T. Abdul-Wahab, Radia Wasi, Asad Yamaguchi, Alyson Yen, Shane Imran, Mir |
author_facet | Dhalla, Arvinder K. Al-Shamsie, Ziad Beraki, Simret Dasari, Anvesh Fung, Leonard C. Fusaro, Laura Garapaty, Anusha Gutierrez, Betsy Gratta, Delia Hashim, Mir Horlen, Kyle Karamchedu, Padma Korupolu, Radhika Liang, Eric Ong, Chang Owyang, Zachary Salgotra, Vasudha Sharma, Shilpy Syed, Baber Syed, Mansoor Vo, April T. Abdul-Wahab, Radia Wasi, Asad Yamaguchi, Alyson Yen, Shane Imran, Mir |
author_sort | Dhalla, Arvinder K. |
collection | PubMed |
description | Biotherapeutics are highly efficacious, but the pain and inconvenience of chronic injections lead to poor patient compliance and compromise effective disease management. Despite innumerable attempts, oral delivery of biotherapeutics remains unsuccessful due to their degradation in the gastrointestinal (GI) environment and poor intestinal absorption. We have developed an orally ingestible robotic pill (RP) for drug delivery, which protects the biotherapeutic drug payload from digestion in the GI tract and auto-injects it into the wall of the small intestine as a safe, pain-free injection since the intestines are insensate to sharp stimuli. The payload is delivered upon inflation of a balloon folded within the RP, which deflates immediately after drug delivery. Here we present results from two clinical studies demonstrating the safety, tolerability and performance of the RP in healthy humans. In the first study, three versions of the RP (A, B and C) were evaluated, which were identical in all respects except for the diameter of the balloon. The RP successfully delivered a biotherapeutic (octreotide) in 3 out of 12 subjects in group A, 10 out of 20 subjects in group B and 16 out of 20 subjects in group C, with a mean bioavailability of 65 ± 9% (based on successful drug deliveries in groups A and B). Thus, reliability of drug delivery with the RP ranged from 25 to 80%, with success rate directly related to balloon size. In a separate study, the deployment of the RP was unaffected by fed or fasting conditions suggesting that the RP may be taken with or without food. These promising clinical data suggest that biotherapeutics currently administered parenterally may be safely and reliably delivered via this versatile, orally ingestible drug delivery platform. GRAPHICAL ABSTRACT: [Image: see text] |
format | Online Article Text |
id | pubmed-8677648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-86776482022-01-04 A robotic pill for oral delivery of biotherapeutics: safety, tolerability, and performance in healthy subjects Dhalla, Arvinder K. Al-Shamsie, Ziad Beraki, Simret Dasari, Anvesh Fung, Leonard C. Fusaro, Laura Garapaty, Anusha Gutierrez, Betsy Gratta, Delia Hashim, Mir Horlen, Kyle Karamchedu, Padma Korupolu, Radhika Liang, Eric Ong, Chang Owyang, Zachary Salgotra, Vasudha Sharma, Shilpy Syed, Baber Syed, Mansoor Vo, April T. Abdul-Wahab, Radia Wasi, Asad Yamaguchi, Alyson Yen, Shane Imran, Mir Drug Deliv Transl Res Original Article Biotherapeutics are highly efficacious, but the pain and inconvenience of chronic injections lead to poor patient compliance and compromise effective disease management. Despite innumerable attempts, oral delivery of biotherapeutics remains unsuccessful due to their degradation in the gastrointestinal (GI) environment and poor intestinal absorption. We have developed an orally ingestible robotic pill (RP) for drug delivery, which protects the biotherapeutic drug payload from digestion in the GI tract and auto-injects it into the wall of the small intestine as a safe, pain-free injection since the intestines are insensate to sharp stimuli. The payload is delivered upon inflation of a balloon folded within the RP, which deflates immediately after drug delivery. Here we present results from two clinical studies demonstrating the safety, tolerability and performance of the RP in healthy humans. In the first study, three versions of the RP (A, B and C) were evaluated, which were identical in all respects except for the diameter of the balloon. The RP successfully delivered a biotherapeutic (octreotide) in 3 out of 12 subjects in group A, 10 out of 20 subjects in group B and 16 out of 20 subjects in group C, with a mean bioavailability of 65 ± 9% (based on successful drug deliveries in groups A and B). Thus, reliability of drug delivery with the RP ranged from 25 to 80%, with success rate directly related to balloon size. In a separate study, the deployment of the RP was unaffected by fed or fasting conditions suggesting that the RP may be taken with or without food. These promising clinical data suggest that biotherapeutics currently administered parenterally may be safely and reliably delivered via this versatile, orally ingestible drug delivery platform. GRAPHICAL ABSTRACT: [Image: see text] Springer US 2021-02-19 2022 /pmc/articles/PMC8677648/ /pubmed/33604838 http://dx.doi.org/10.1007/s13346-021-00938-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Dhalla, Arvinder K. Al-Shamsie, Ziad Beraki, Simret Dasari, Anvesh Fung, Leonard C. Fusaro, Laura Garapaty, Anusha Gutierrez, Betsy Gratta, Delia Hashim, Mir Horlen, Kyle Karamchedu, Padma Korupolu, Radhika Liang, Eric Ong, Chang Owyang, Zachary Salgotra, Vasudha Sharma, Shilpy Syed, Baber Syed, Mansoor Vo, April T. Abdul-Wahab, Radia Wasi, Asad Yamaguchi, Alyson Yen, Shane Imran, Mir A robotic pill for oral delivery of biotherapeutics: safety, tolerability, and performance in healthy subjects |
title | A robotic pill for oral delivery of biotherapeutics: safety, tolerability, and performance in healthy subjects |
title_full | A robotic pill for oral delivery of biotherapeutics: safety, tolerability, and performance in healthy subjects |
title_fullStr | A robotic pill for oral delivery of biotherapeutics: safety, tolerability, and performance in healthy subjects |
title_full_unstemmed | A robotic pill for oral delivery of biotherapeutics: safety, tolerability, and performance in healthy subjects |
title_short | A robotic pill for oral delivery of biotherapeutics: safety, tolerability, and performance in healthy subjects |
title_sort | robotic pill for oral delivery of biotherapeutics: safety, tolerability, and performance in healthy subjects |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677648/ https://www.ncbi.nlm.nih.gov/pubmed/33604838 http://dx.doi.org/10.1007/s13346-021-00938-1 |
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