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Abstract

PHARMACOKINETIC AND PHARMACODYNAMIC STUDY OF NEWLY SYNTHESIZED MUTUAL AZO PRODRUGS OF AMOXICILLIN AND 5-AMINO SALICYLIC ACID AGAINST ULCERATIVE COLITIS

Deepika Nagpal*, Nidhi Agrawal, Arun Nanda and D.P. Pathak

ABSTRACT

Ulcerative colitis (UC) is an inflammatory syndrome of gastrointestinal tract. Indeed, numerous anti-inflammatory therapeutic strategies are available in market but the clinical prevalence of this chronic disorder is still high. Several existing therapeutic strategies are based on the targeting of colon which is the largest area of gastrointestinal tract and hence may be potential delivery systems for targeted specific drug. Some study reveals that polymeric azo compounds could be employed for colon targeting, since reduction and splitting of azo bond only occurs in large intestine, which increase the probability of sitespecificity for drug. The present study investigates the use of azo prodrug of 5-ASA and amoxicillin for targeted oral drug delivery to the experimentally inflamed tissue of colon in IBD. Induction of colitis by acetic acid in rats is one of standardized methods to produce an experimental model of inflammatory bowel disease for assessing in vivo characterization of the azo carrier system under the influence of chronic inflammatory symptoms. Reduction of vascular permeability, cellular infiltration in the mucosa, MPO activity and increase antioxidant property of amoxicillin suggest its potential role against UC. 5-ASA prodrug (SAP) has evaluated for targeted delivery in colon by studying the release potential in rat fecal matter. Rate of ulcerogenic activity, colon/body weight ratio and histological report has evaluated. SAP shows lower ulcer index as compare to oral addministeration of 5-ASA which shows negligible release in upper GI trat. In vivo treatment with SAP results significant decrease in extent and severity of colonic damage. Moreover the histological evaluation also reveals the potential protection of SAP.

Keywords: Ulcerative colitis, Crohn's disease, Inflammation, 5-amino salicylic acid, GIT, Azo prodrug.


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