Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 11، دوره 23، شماره 6، شهریور 2020، صفحه 781-787 اصل مقاله (589.63 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2020.41152.9736 | ||
| نویسندگان | ||
| Fatemeh Sadeghi1، 2؛ Atie Eidizade1؛ Farinaz Saremnejad3؛ Farzin Hadizadeh4، 5؛ Elham Khodaverdi1، 2؛ Abbas Akhgari* 1، 2 | ||
| 1Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran | ||
| 2Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran | ||
| 3Department of Food Science and Technology, Ferdowsi University of Mashhad, Mashhad, Iran | ||
| 4Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran | ||
| 5Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran | ||
| چکیده | ||
| 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. | ||
| کلیدواژهها | ||
| 4-aminosalicylic acid؛ Azo linkage؛ IBD؛ PEGylated prodrug؛ Prodrug | ||
| مراجع | ||
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