Potent anti-inflammatory agents have been engineered as prodrugs to target only the colonic area
GiiAnt, the Gastrointestinal-induced Anti-inflammatory technology, is a unique local delivery strategy that capitalize on the bacterial activity of the gut microbiota to bioactivate and specifically release the active principle at the site of inflammation while minimizing any potential side effects from systemic exposure.
1. Colon-Specific Prodrug
The prodrug is conveniently orally-dosed but poorly absorbed in the upper GIT. Furthermore, the low bacterial activity found in the small intestine, prevents the premature release of the parent active principle. This allows most of the dose to reach the lower bowel while minimizing systemic exposure.
2. Gut Bacterial Activation
The sharp gradient of bacterial activity between the upper GIT and the lower bowel is used as a very specific trigger to bioactivate the prodrug in the colonic area.
3. Active Principle Release
The enzymatic breakdown of the covalent bound linking the parent anti-inflammatory agent and the promoiety releases the active principle. This local delivery represents the best strategy to avoid systemic immunosuppression while maximizing the drug concentration at the site of inflammation.
Dynamic Release System
The ultimate level of precision for drug delivery
The concept of Dynamic Release System (disease-inducible bioactivation) is illustrated below. Even though the prodrug is bioactivated in the non-inflamed area (A), some of it keep progressing to the active site of inflammation (B) where the presence of blood, from colon mucosa ulceration, activates the prodrug. This results in a significant increase in the rate of enzymatic break down and therefore, a higher local concentration of the parent anti-inflammatory agent.