Colon-specific delivery bowel diseases

The same strategy was applied in colon-specific delivery of two corticosteroids used to treat inflammatory bowel disease [20][21], Indeed, budeso-nide /3-D-glucuronide and dexamethasone /3-D-glucuronide underwent ready hydrolysis in the luminal contents of rat colon and caecum. Rat mucosal homogenates were less active, and hydrolysis in human fecal samples was quite low. Based on these and other studies, the prodrugs were found to be suitable candidates for delivery of corticosteroids to the large intestine. 

This time controlled release tablet with a designated lag time followed by a rapid release may provide an alternative to site-specific delivery of drugs with optimal absorption windows or colonic delivery of drugs that are sensitive to low pH or enzyme action for the treatment of localized conditions such as ulcerative colitis, Crohn s disease, and irritable bowel syndrome (IBS). Also, by controlling a predetermined lag time of drug from dosage form, the release behavior can be matched with the body s circadian rhythm pattern in chronotherapy. 

Site-specific delivery and release of drugs will not only be useful to achieve systemic therapeutic effects (after absorption), but also topical applications, for instance for the treatment of inflammatory bowel disease, ulcerative colitis, and colon cancer, to name the most prevalent. 

A major indication for colon-specific drug delivery is in the treatment of local disorders of the colon, such as inflammatory bowel disease (IBD which includes ulcerative colitis and Crohn s disease) and carcinoma of the colon. The colon can also be used as an absorption site for the delivery of drags to the systemic circulation. Although absorption from the colon is generally considerably lower than from the small intestine, systemic drag delivery via the colon is associated with a number of advantages, including ... 

Membranes play a fundamental role also in the colon-specific drug delivery systems. This administration route, whose advantages have been well recognized and documented [158], provides more effective therapy of colon-related diseases such as irritable bowel syndrome and inflammatory bowel disease (IBD) including Crohn s disease and ulcerative colitis. 

An attempt is made to synthesise a polymer that will act as a controlled delivery device in targeting specific areas, such as the colon, over an extended period of time. The polymers being synthesised, polyanhydride esters, are composed of alkyl chains linked by ester bonds to aromatic moieties, specifically salicylic acid - the active component of aspirin. With the medicinal properties attributed to salicyclic acid and the ease of metabolism, the incorporation of this compound into a polymer backbone yields a polymeric prodrug that may have potential in a variety of applications, in particular, inflammatory bowel disease. For these reasons, a synthetic scheme that yields the desired polyanhydride esters is designed. Characterisation of the polymers is performed and presented along with preliminary in vitro and possible... 

S.S. Dhaneshwar, N. Gairola, M. Kandpal, G. Vadnerkar, L. Bhatt, B. Rathi, and S.S. Kadam, Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrugs of 5-ami-nosalicylic acid for colon-specific drug delivery in inflammatory bowel disease, Eur. J. Med. Chem. 44 3922-3929, 2009. 

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