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Systems Biology and Peptide Engineering to Overcome Absorption Barriers for Oral Peptide Delivery: Dosage Form Optimization Case Study Preceding Clinical Translation

Oral delivery of peptides and biological molecules promises significant benefits to patients as an alternative to daily injections, but the development of these formulations is challenging due to their low bioavailability and high pharmacokinetic variability. Our earlier work focused on the discover...

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Autores principales: Tyagi, Puneet, Patel, Chandresh, Gibson, Kimberly, MacDougall, Fiona, Pechenov, Sergei Y., Will, Sarah, Revell, Jefferson, Huang, Yue, Rosenbaum, Anton I., Balic, Kemal, Maharoof, Umar, Grimsby, Joseph, Subramony, J. Anand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610252/
https://www.ncbi.nlm.nih.gov/pubmed/37896196
http://dx.doi.org/10.3390/pharmaceutics15102436
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author Tyagi, Puneet
Patel, Chandresh
Gibson, Kimberly
MacDougall, Fiona
Pechenov, Sergei Y.
Will, Sarah
Revell, Jefferson
Huang, Yue
Rosenbaum, Anton I.
Balic, Kemal
Maharoof, Umar
Grimsby, Joseph
Subramony, J. Anand
author_facet Tyagi, Puneet
Patel, Chandresh
Gibson, Kimberly
MacDougall, Fiona
Pechenov, Sergei Y.
Will, Sarah
Revell, Jefferson
Huang, Yue
Rosenbaum, Anton I.
Balic, Kemal
Maharoof, Umar
Grimsby, Joseph
Subramony, J. Anand
author_sort Tyagi, Puneet
collection PubMed
description Oral delivery of peptides and biological molecules promises significant benefits to patients as an alternative to daily injections, but the development of these formulations is challenging due to their low bioavailability and high pharmacokinetic variability. Our earlier work focused on the discovery of MEDI7219, a stabilized, lipidated, glucagon-like peptide 1 agonist peptide, and the selection of sodium chenodeoxycholate (Na CDC) and propyl gallate (PG) as permeation enhancer combinations. We hereby describe the development of the MEDI7219 tablet formulations and composition optimization via in vivo studies in dogs. We designed the MEDI7219 immediate-release tablets with the permeation enhancers Na CDC and PG. Immediate-release tablets were coated with an enteric coating that dissolves at pH ≥ 5.5 to target the upper duodenal region of the gastrointestinal tract and sustained-release tablets with a Carbopol bioadhesive polymer were coated with an enteric coating that dissolves at pH ≥ 7.0 to provide a longer presence at the absorption site in the gastrointestinal tract. In addition to immediate- and enteric-coated formulations, we also tested a proprietary delayed release erodible barrier layer tablet (OralogiK(TM)) to deliver the payload to the target site in the gastrointestinal tract. The design of tablet dosage forms based on the optimization of formulations resulted in up to 10.1% absolute oral bioavailability in dogs with variability as low as 26% for MEDI7219, paving the way for its clinical development.
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spelling pubmed-106102522023-10-28 Systems Biology and Peptide Engineering to Overcome Absorption Barriers for Oral Peptide Delivery: Dosage Form Optimization Case Study Preceding Clinical Translation Tyagi, Puneet Patel, Chandresh Gibson, Kimberly MacDougall, Fiona Pechenov, Sergei Y. Will, Sarah Revell, Jefferson Huang, Yue Rosenbaum, Anton I. Balic, Kemal Maharoof, Umar Grimsby, Joseph Subramony, J. Anand Pharmaceutics Article Oral delivery of peptides and biological molecules promises significant benefits to patients as an alternative to daily injections, but the development of these formulations is challenging due to their low bioavailability and high pharmacokinetic variability. Our earlier work focused on the discovery of MEDI7219, a stabilized, lipidated, glucagon-like peptide 1 agonist peptide, and the selection of sodium chenodeoxycholate (Na CDC) and propyl gallate (PG) as permeation enhancer combinations. We hereby describe the development of the MEDI7219 tablet formulations and composition optimization via in vivo studies in dogs. We designed the MEDI7219 immediate-release tablets with the permeation enhancers Na CDC and PG. Immediate-release tablets were coated with an enteric coating that dissolves at pH ≥ 5.5 to target the upper duodenal region of the gastrointestinal tract and sustained-release tablets with a Carbopol bioadhesive polymer were coated with an enteric coating that dissolves at pH ≥ 7.0 to provide a longer presence at the absorption site in the gastrointestinal tract. In addition to immediate- and enteric-coated formulations, we also tested a proprietary delayed release erodible barrier layer tablet (OralogiK(TM)) to deliver the payload to the target site in the gastrointestinal tract. The design of tablet dosage forms based on the optimization of formulations resulted in up to 10.1% absolute oral bioavailability in dogs with variability as low as 26% for MEDI7219, paving the way for its clinical development. MDPI 2023-10-09 /pmc/articles/PMC10610252/ /pubmed/37896196 http://dx.doi.org/10.3390/pharmaceutics15102436 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tyagi, Puneet
Patel, Chandresh
Gibson, Kimberly
MacDougall, Fiona
Pechenov, Sergei Y.
Will, Sarah
Revell, Jefferson
Huang, Yue
Rosenbaum, Anton I.
Balic, Kemal
Maharoof, Umar
Grimsby, Joseph
Subramony, J. Anand
Systems Biology and Peptide Engineering to Overcome Absorption Barriers for Oral Peptide Delivery: Dosage Form Optimization Case Study Preceding Clinical Translation
title Systems Biology and Peptide Engineering to Overcome Absorption Barriers for Oral Peptide Delivery: Dosage Form Optimization Case Study Preceding Clinical Translation
title_full Systems Biology and Peptide Engineering to Overcome Absorption Barriers for Oral Peptide Delivery: Dosage Form Optimization Case Study Preceding Clinical Translation
title_fullStr Systems Biology and Peptide Engineering to Overcome Absorption Barriers for Oral Peptide Delivery: Dosage Form Optimization Case Study Preceding Clinical Translation
title_full_unstemmed Systems Biology and Peptide Engineering to Overcome Absorption Barriers for Oral Peptide Delivery: Dosage Form Optimization Case Study Preceding Clinical Translation
title_short Systems Biology and Peptide Engineering to Overcome Absorption Barriers for Oral Peptide Delivery: Dosage Form Optimization Case Study Preceding Clinical Translation
title_sort systems biology and peptide engineering to overcome absorption barriers for oral peptide delivery: dosage form optimization case study preceding clinical translation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610252/
https://www.ncbi.nlm.nih.gov/pubmed/37896196
http://dx.doi.org/10.3390/pharmaceutics15102436
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