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• W2090848746 abstract "Chronic inflammatory bowel diseases (IBDs) are still waiting for improved and innovative therapeutic treatments, which can overcome the limits of the current approaches. Since IBDs affect mainly the lower tract of the intestine, a localized therapy in the colon tract will avoid most of the problems caused by systemic or poor selective therapies. Particularly promising are the advance drug delivery systems that can reach specific colon delivery, thus guaranteeing active agent release only at the site of action. This approach can meet two aims at the same time, first of all the drug will not affect healthy tissue and second a lower drug dose may be used because all the administered active agent will reach the target. To obtain a specific colon delivery we exploited the azoreductase enzymes, selectively present only in colon, by inserting an azo linker between a selected drug and a macromolecular carrier. The drug employed is mesalazine, a well know and used agent against IBDs. Poly(ethylene glycol) (PEG), of different molecular weights and structures, was used as carrier. Three different conjugates were synthesized and characterized, and the most promising one, with highest drug loading thanks to the use of diamino PEG of 4 kDa, was further investigated in vitro on mouse colonic epithelial cells (CMT-9) and in vivo on model mice with induced colitis. The data presented here demonstrate that PEG conjugation of mesalazine prevents drug release and absorption in upper intestine, after oral administration of the conjugates, and that the azo linker ensures a good drug release in the colon tract. The results in vivo take into consideration mice bodyweight gain, tissue histology and interleukin-2β as an index of inflammation. These parameters, all together, demonstrated the conjugate effectiveness against the controls." @default.
• W2090848746 created "2016-06-24" @default.
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• W2090848746 date "2009-02-01" @default.
• W2090848746 modified "2023-10-12" @default.
• W2090848746 title "Poly(ethylene glycol)-mesalazine conjugate for colon specific delivery" @default.
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• W2090848746 doi "https://doi.org/10.1016/j.ijpharm.2008.09.058" @default.
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