Bioinspired oral insulin delivery system using yeast microcapsules

Type 1 diabetes mellitus (DM) is a metabolic disorder associated with impaired carbohydrate metabolism. We present a promising bioinspired approach against type 1 DM using yeast microcapsule (YMC). The glucan component in the outer shell of baker's yeast undergoes receptor-mediated uptake by phagocytic cells through M cell-mediated endocytosis. Thus, a drug can be expected to be delivered to the systemic circulation via lymphatic transport if it is attached to the surface of YMC. For the first time, this possibility has been explored by surface loading of insulin onto YMC. The electrostatic interaction between oppositely charged YMC and insulin resulted in the formation of insulin-loaded yeast microcapsule (IYMC) which was confirmed by fluorescence imaging. Alginate coating provided to IYMC protects YMC from the harsh environment of the gastrointestinal tract and prevents the degradation of insulin in IYMC. Cellular uptake of FITC conjugated IYMC by RAW macrophages confirmed the proposed mechanism of insulin uptake. Moreover, an in vitro method using YMC-imprinted gel was developed for insulin release study from the bioinspired system. Molecular docking studies proved the interaction of insulin with β-glucan and alginate. A significant hypoglycemic effect was observed after oral administration of the alginate coated insulin-loaded yeast microcapsule (AL-IYMC) in diabetic rats. The AL-IYMCs could serve as a promising approach towards the oral delivery of insulin.