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Modern Prodrug Design for Targeted Oral Drug Delivery

The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilici...

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Autores principales: Dahan, Arik, Zimmermann, Ellen M., Ben-Shabat, Shimon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271014/
https://www.ncbi.nlm.nih.gov/pubmed/25317578
http://dx.doi.org/10.3390/molecules191016489
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author Dahan, Arik
Zimmermann, Ellen M.
Ben-Shabat, Shimon
author_facet Dahan, Arik
Zimmermann, Ellen M.
Ben-Shabat, Shimon
author_sort Dahan, Arik
collection PubMed
description The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodrug design considers molecular/cellular factors, e.g., membrane influx/efflux transporters and cellular protein expression and distribution. This novel targeted-prodrug approach is aimed to exploit carrier-mediated transport for enhanced intestinal permeability, as well as specific enzymes to promote activation of the prodrug and liberation of the free parent drug. The purpose of this article is to provide a concise overview of this modern prodrug approach, with useful successful examples for its utilization. In the past the prodrug approach used to be viewed as a last option strategy, after all other possible solutions were exhausted; nowadays this is no longer the case, and in fact, the prodrug approach should be considered already in the very earliest development stages. Indeed, the prodrug approach becomes more and more popular and successful. A mechanistic prodrug design that aims to allow intestinal permeability by specific transporters, as well as activation by specific enzymes, may greatly improve the prodrug efficiency, and allow for novel oral treatment options.
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spelling pubmed-62710142018-12-27 Modern Prodrug Design for Targeted Oral Drug Delivery Dahan, Arik Zimmermann, Ellen M. Ben-Shabat, Shimon Molecules Concept Paper The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodrug design considers molecular/cellular factors, e.g., membrane influx/efflux transporters and cellular protein expression and distribution. This novel targeted-prodrug approach is aimed to exploit carrier-mediated transport for enhanced intestinal permeability, as well as specific enzymes to promote activation of the prodrug and liberation of the free parent drug. The purpose of this article is to provide a concise overview of this modern prodrug approach, with useful successful examples for its utilization. In the past the prodrug approach used to be viewed as a last option strategy, after all other possible solutions were exhausted; nowadays this is no longer the case, and in fact, the prodrug approach should be considered already in the very earliest development stages. Indeed, the prodrug approach becomes more and more popular and successful. A mechanistic prodrug design that aims to allow intestinal permeability by specific transporters, as well as activation by specific enzymes, may greatly improve the prodrug efficiency, and allow for novel oral treatment options. MDPI 2014-10-14 /pmc/articles/PMC6271014/ /pubmed/25317578 http://dx.doi.org/10.3390/molecules191016489 Text en © 2014 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Concept Paper
Dahan, Arik
Zimmermann, Ellen M.
Ben-Shabat, Shimon
Modern Prodrug Design for Targeted Oral Drug Delivery
title Modern Prodrug Design for Targeted Oral Drug Delivery
title_full Modern Prodrug Design for Targeted Oral Drug Delivery
title_fullStr Modern Prodrug Design for Targeted Oral Drug Delivery
title_full_unstemmed Modern Prodrug Design for Targeted Oral Drug Delivery
title_short Modern Prodrug Design for Targeted Oral Drug Delivery
title_sort modern prodrug design for targeted oral drug delivery
topic Concept Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271014/
https://www.ncbi.nlm.nih.gov/pubmed/25317578
http://dx.doi.org/10.3390/molecules191016489
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