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Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug

OBJECTIVE(S): 4-aminosalicylic acid (4-ASA) is an isomer of mesalazine that has recently been shown to be effective against inflammatory bowel disease (IBD), and more specifically, ulcerative colitis. However, the majority of orally administered 4-ASA is readily and extensively absorbed from the sto...

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Autores principales: Sadeghi, Fatemeh, Eidizade, Atie, Saremnejad, Farinaz, Hadizadeh, Farzin, Khodaverdi, Elham, Akhgari, Abbas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mashhad University of Medical Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351447/
https://www.ncbi.nlm.nih.gov/pubmed/32695295
http://dx.doi.org/10.22038/ijbms.2020.41152.9736
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author Sadeghi, Fatemeh
Eidizade, Atie
Saremnejad, Farinaz
Hadizadeh, Farzin
Khodaverdi, Elham
Akhgari, Abbas
author_facet Sadeghi, Fatemeh
Eidizade, Atie
Saremnejad, Farinaz
Hadizadeh, Farzin
Khodaverdi, Elham
Akhgari, Abbas
author_sort Sadeghi, Fatemeh
collection PubMed
description OBJECTIVE(S): 4-aminosalicylic acid (4-ASA) is an isomer of mesalazine that has recently been shown to be effective against inflammatory bowel disease (IBD), and more specifically, ulcerative colitis. However, the majority of orally administered 4-ASA is readily and extensively absorbed from the stomach and small intestine, so only a small amount is transported to the colon. A mutual ester and azo prodrug of 4-ASA was synthesized with polyethylene glycol (PEG) and dimethylaniline, respectively , to overcome this issue. MATERIALS AND METHODS: The 4-ASA prodrug was synthesized via a two-step process and then characterized by 1H-NMR. The stability of the prodrug was evaluated in simulated gastric fluid (pH 1.2). Furthermore, the in vitro release profiles of the drug conjugate was evaluated at pH 1.2, as well as pH 6.8 in the absence or presence of rat cecal content. RESULTS: The prepared prodrug was stable at pH 1.2, indicating that it could be protected from the acidic environment of the stomach. Also, the results of drug release at pH 6.8 showed that the amount of 4-ASA released was 63% within 12 hr in the absence of rat cecal content, while in the presence of rat cecal content, 97% of 4-ASA was released from the prodrug in 6 hr. CONCLUSION: Overall, the synthesized PEGylated azo-based 4-ASA prodrug could be a potential candidate for targeted drug delivery to the inflamed gut tissue in IBD.
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spelling pubmed-73514472020-07-20 Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug Sadeghi, Fatemeh Eidizade, Atie Saremnejad, Farinaz Hadizadeh, Farzin Khodaverdi, Elham Akhgari, Abbas Iran J Basic Med Sci Original Article OBJECTIVE(S): 4-aminosalicylic acid (4-ASA) is an isomer of mesalazine that has recently been shown to be effective against inflammatory bowel disease (IBD), and more specifically, ulcerative colitis. However, the majority of orally administered 4-ASA is readily and extensively absorbed from the stomach and small intestine, so only a small amount is transported to the colon. A mutual ester and azo prodrug of 4-ASA was synthesized with polyethylene glycol (PEG) and dimethylaniline, respectively , to overcome this issue. MATERIALS AND METHODS: The 4-ASA prodrug was synthesized via a two-step process and then characterized by 1H-NMR. The stability of the prodrug was evaluated in simulated gastric fluid (pH 1.2). Furthermore, the in vitro release profiles of the drug conjugate was evaluated at pH 1.2, as well as pH 6.8 in the absence or presence of rat cecal content. RESULTS: The prepared prodrug was stable at pH 1.2, indicating that it could be protected from the acidic environment of the stomach. Also, the results of drug release at pH 6.8 showed that the amount of 4-ASA released was 63% within 12 hr in the absence of rat cecal content, while in the presence of rat cecal content, 97% of 4-ASA was released from the prodrug in 6 hr. CONCLUSION: Overall, the synthesized PEGylated azo-based 4-ASA prodrug could be a potential candidate for targeted drug delivery to the inflamed gut tissue in IBD. Mashhad University of Medical Sciences 2020-06 /pmc/articles/PMC7351447/ /pubmed/32695295 http://dx.doi.org/10.22038/ijbms.2020.41152.9736 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Sadeghi, Fatemeh
Eidizade, Atie
Saremnejad, Farinaz
Hadizadeh, Farzin
Khodaverdi, Elham
Akhgari, Abbas
Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug
title Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug
title_full Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug
title_fullStr Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug
title_full_unstemmed Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug
title_short Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug
title_sort synthesis of a novel pegylated colon-specific azo-based 4- aminosalicylic acid prodrug
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351447/
https://www.ncbi.nlm.nih.gov/pubmed/32695295
http://dx.doi.org/10.22038/ijbms.2020.41152.9736
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