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Colon-targeted drug delivery

Colon-targeted drug delivery systems are formulations intended to protect the drug from delivery in the upper gastrointestinal track (mouth to ileum) and deliver the drug when the dosage form reaches colon.

Need for targeting colon

These delivery systems are utilized when colon is the target tissue for action of drug, such as in case of Inflammatory bowl disease, ulcerative colitis, crohn’s disease and colon cancer (1). Such targeted delivery allows for minimizing systemic absorption-associated dilution of drug and potential side effects from off-target exposure.

Mechanisms of targeting delivery to colon

There are 2 predominant mechanisms for targeting drug delivery to colon. 1) pH-responsive 2) microbial enzyme-responsive.

pH-responsive delivery systems

Utilizing the known increase in pH at the end of small intestine, these delivery systems are often designed with pH-sensitive polymers that dissolve at close to neutral pH, generally present at the end of small intestine. pH-responsive polymers such as copolymers of methacrylic acid and methyl methacrylate (e.g., Eudragit S100, Eudragit FS), hydroxypropyl methyl-cellulose phthalate (HPMCP)50 and 55, Cellulose acetate phthalate are utilized for this approach. These polymers are water-insoluble in upper small intestine so in a dosage form, they protect the drug from release in low pH. When the dosage form transits to ileum, the pH rises to close to neutral, dissolving the polymer and thereby, releasing the drug in proximity of colon. These delivery systems are prone to failure (to release) when the GI pH is perturbed due to change in GI motility, disease state, etc.

Microbial enzyme-responsive delivery systems

Colon has very high proportion of bacteria, often being able to digest materials not digestible by human enzymes, such as, soluble fibers and resistant starches. Microbial-based delivery systems incorporate such bacterially-digestible material (e.g., chitosan, pectin, hyaluronic acid, high amylose starch, guar gum) in a coating that protects the drug from release in aqueous environment. Colonic-bacterial digestion of such materials results in weaking of protection around the drug and therefore, release of the drug.