Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1785128209121017856 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10610252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT tyagipuneet systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation AT patelchandresh systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation AT gibsonkimberly systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation AT macdougallfiona systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation AT pechenovsergeiy systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation AT willsarah systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation AT revelljefferson systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation AT huangyue systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation AT rosenbaumantoni systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation AT balickemal systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation AT maharoofumar systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation AT grimsbyjoseph systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation AT subramonyjanand systemsbiologyandpeptideengineeringtoovercomeabsorptionbarriersfororalpeptidedeliverydosageformoptimizationcasestudyprecedingclinicaltranslation |