Preparation and characterization of an amphoteric chitosan derivative employing trimellitic anhydride chloride and its potential for colon targeted drug delivery system

Trimellitic anhydride chloride was used to generate a water soluble amphoteric chitosan derivative (CTAA). CTAA was combined with alginate to facilitate direct targeting of 5-FU to the colon. The structure of CTAA was characterized by FTIR, 1H/13C NMR and HSQC. The physical properties of the CTAA hydrogel were analyzed by scanning electron microscopy, X-ray diffraction and thermogravimetry. Inhibition of a pancreatic enzyme's activity and cytotoxicity studies of CTAA were also carried out. Sodium alginate was mixed with CTAA to form a polyelectrolyte complex film and resulted in improved controlled drug release. Swelling characteristics of the films as a function of pH were also investigated. An optimized formulation was exposed to conditions simulating the stomach, small intestine, and colon. The CTAA/alginate formulation used in this preliminary study presents potential for at least 28% of ingested 5-FU to arrive at the colon ready for release by colonic enzymes. Films were chosen in the study to severely stretch the capabilities of the CTAA/alginate system. The system nevertheless will need modifying for in vivo delivery to the colon.

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