Thiolated Eudragit-based Nanoparticles for Oral Insulin Delivery: Preparation, Characterization, and Evaluation Using Intestinal Epithelial Cells In Vitro

This work deals with the synthesis of insulin loaded nanoparticles (NPs) composed of thiolated Eudragit L100 (Eul‐cys) and reduced glutathione (GSH) as potential nanocarriers for oral delivery of insulin. Perfectly spherical NPs with an average particle size of nearly 200–300 nm are prepared. The insulin release from Eul‐cys/GSH and Eul‐cys NPs in PBS (pH 7.4) shows that GSH can slightly decrease the release rate of insulin. Eul‐cys in combination with GSH or sodium caprate (SC) is evaluated for its permeation enhancing effect of FITC‐insulin using the Caco‐2 monolayer and Caco‐2/HT29‐MTX co‐cultured cells models. SC results in greater permeation enhancement compared to GSH. However, GSH proves to be less toxic. Paracellular transport of insulin represents the main mechanism by which the NPs facilitate insulin permeation through the intestinal epithelium, whereas a number of NPs are also taken up by the cells and release insulin within the cells. Novel nanoparticles composed of Eudragit L100‐cysteine (Eul‐cys) and reduced glutathione (GSH) are prepared as potential nanocarriers for the oral delivery of insulin. The permeation enhancement of GSH is evaluated by Caco‐2 and Caco‐2/HT29‐MTX co‐cultured cells in vitro, which is compared to sodium caprate (SC). The results indicate that the mucus layer may be a barrier for transportation of thiolated nanoparticles, and the paracellular route may represent the main mechanism by which nanoparticles facilitate insulin permeation.