Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1783557446134923264 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7351447 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Mashhad University of Medical Sciences |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT sadeghifatemeh synthesisofanovelpegylatedcolonspecificazobased4aminosalicylicacidprodrug AT eidizadeatie synthesisofanovelpegylatedcolonspecificazobased4aminosalicylicacidprodrug AT saremnejadfarinaz synthesisofanovelpegylatedcolonspecificazobased4aminosalicylicacidprodrug AT hadizadehfarzin synthesisofanovelpegylatedcolonspecificazobased4aminosalicylicacidprodrug AT khodaverdielham synthesisofanovelpegylatedcolonspecificazobased4aminosalicylicacidprodrug AT akhgariabbas synthesisofanovelpegylatedcolonspecificazobased4aminosalicylicacidprodrug |