Physicochemical and Morphological Transformations of Chitosan Nanoparticles across the Gastrointestinal Tract and Cellular Toxicity in an In Vitro Model of the Small Intestinal Epithelium.

Abstract

Nanoscale chitosan materials exhibit size-specific properties that make them useful in agri-food and biomedical applications. Chitosan nanoparticles (Chnps) are being explored as nanocarrier platforms to increase oral bioavailability of drugs and nutraceuticals, but little is known of their fate and transformations in the gastrointestinal tract (GIT) or of their potential toxicity. Here, the GIT fate and cytotoxicity of Chnps, soluble starch-coated Chnps (SS-Chnps), and bulk chitosan powder (Chp), were assessed using a 3-phase simulated digestion and an in vitro cellular small intestinal epithelium model. Physico-chemical characterization revealed dissolution of Chp, but not of Chnps or SS-Chnps, during the gastric phase of digestion, stability of the starch coating of SS-Chnps in the oral and gastric phases, and agglomeration of all materials during the small intestinal phase. A slight but significant (10%, p < 0.01) increase in cytotoxicity (LDH release) was observed with exposure to digested Chnps but not Chp or SS-Chnps.