Aggrandizing Delivery of Nalidixic Acid to Colon Employing A Targeted Prodrug Approach: Synthesis and in vivo Evaluation

Objective: The project was aimed at synthesizing and characterizing amino acid conjugate of Nalidixic acid (NA) that is expected to enhance solubility without affecting permeability and is capable of delivering NA to colon without significant reversion of prodrug in gastrointestinal conditions. Methods: Thus, nalidixic acid-L-tryptophan conjugate (NA-TRYPh) was prepared by conventional coupling method and the prodrug was characterized by FTIR, HPLC, NMR, FAB mass and elemental analysis. The conjugate was then subjected to selected pharmaceutical preformulation studies like aqueous solubility analysis and pH partition studies. Results: These studies established 1.24 folds higher solubility of the NA-TRYPh over NA in phosphate buffer pH 7.4 without compromising its partitioning ability. The in vitro stability studies suggested its potential of safe transit to colon where the moiety is capable of reverting to 90.52% NA after 48 hrs of the experiment. In vivo evaluation of NA-TRYPh in an experimentally induced colitis established its efficacy an anti-inflammatory prodrug moiety that was supported by histological studies. In addition to its ability to control colonic ulcers NA-TRYPh demonstrated insignificant (P >0.05) gastric ulcerogenic potential. Colonic MPO activity for NA-TRYPh in mU/100 mg tissue was found to be 44.97 which were much less than plain NA (75.5). Conclusion: Conclusively, the conjugate when suitably formulated can be considered as therapeutically efficacious drug delivery system with fewer pharmaceutical limitations