Application of Prodrugs to Inflammatory Diseases of the Gut

Abstract

Oral delivery is the most common and preferred route of drug administrationalthough the digestive tract exhibits several obstacles to drug delivery including motilityand intraluminal pH profiles. The gut milieu represents the largest mucosal surfaceexposed to microorganisms with 1010-12 colony forming bacteria/g of colonic content.Approximately, one third of fecal dry matter is made of bacteria/ bacterial components.Indeed, the normal gut microbiota is responsible for healthy digestion of dietary fibers(polysaccharides) and fermentation of short chain fatty acids such as acetate and butyratethat provide carbon sources (fuel) for these bacteria. Inflammatory bowel disease (IBD)results in breakage of the mucosal barrier, an altered microbiota and dysregulated gutimmunity. Prodrugs that are chemically constructed to target colonic release or aredegraded specifically by colonic bacteria, can be useful in the treatment of IBD. Thisreview describes the progress in digestive tract prodrug design and delivery in light of gutmetabolic activities.

Keywords

• Inflammatory bowel disease
• Digestive tract
• Drug delivery
• microbiota
• 5-Aminosalicylic acid
• Mycophenolate mofetil
• Cysteine and Glutathione prodrugs