Chitosan/Sodium Tripolyphosphate Microemulsion Enhanced Oral Insulin Delivery via Intestinal Lymphoid

Abstract Oral insulin delivery systems are currently being explored as the best alternative to subcutaneous injections, aiming to overcome gastrointestinal barriers and achieve efficient oral insulin delivery. This study presents a microemulsion delivery system that utilizes chitosan/sodium tripolyphosphate (CS/STPP) to enhance the stability of kernel‐loaded insulin and increase bioavailability via intestinal absorption and lymphatic transport. The insulin/chitosan/sodium tripolyphosphate‐microemulsion (Ins/CS/STPP‐ME) is a particle size of (81.03 ± 7.19) nm and a polydispersity index (PDI) of (0.313 ± 0.013). Infrared spectroscopy confirms insulin encapsulation. Ins/CS/STPP‐ME exhibits favorable stability and releasesproperties in gastrointestinal fluids, retaining a maximum of (53.076 ± 12.587)% insulin in a pepsin environment and (62.982 ± 13.105)% in a trypsin environment after 60 min. In vivo studies have demonstrated that the addition of CS/STPP to the internal phase of Ins/CS/STPP‐ME results in a rapid onset of action and sustained hypoglycaemic effect in diabetic rats. Lymphatic blockade by cycloheximide verified Ins/CS/STPP‐ME and its ability to cross the gut and enter the bloodstream via lymphatic transport. This work demonstrates that Ins/CS/STPP‐ME can stabilize proteins in the gastrointestinal environment, facilitate lymphatic absorption, enhance bioavailability, and provide longer‐lasting hypoglycemic effects, thus providing the possibility for oral biomacromolecule delivery.