Objective: Oral administration of insulin is a potential candidate for managing diabetes. However, it is obstructed by the gastrointestinal tract barriers resulting in negligible oral bioavailability.

Methods: This investigation presents a novel nanocarrier platform designed to address these challenges. In this regard, the process involved amination of sodium alginate by ethylene diamine, followed by its conjugation with deoxycholic acid.

Results: The resulting DCA@Alg@INS nanocarrier revealed a significantly high insulin loading content of 63.6 ± 1.03% and encapsulation efficiency of 87.6 ± 3.84%, with a particle size of 206 nm and zeta potentials of -3 mV. In vitro studies showed sustained and pH-dependent release profiles of insulin from nanoparticles. In vitro cellular studies, confocal laser scanning microscopy and flow cytometry analysis confirmed the successful attachment and internalization of DCA@Alg@INS nanoparticles in Caco-2 cells. Furthermore, the DCA@Alg@INS demonstrated a superior capacity for cellular uptake and permeability coefficient relative to the insulin solution, exhibiting sixfold and 4.94-fold enhancement, respectively. According to the uptake mechanism studies, the results indicated that DCA@Alg@INS was mostly transported through an energy-dependent active pathway since the uptake of DCA@Alg@INS by cells was significantly reduced in the presence of NaN3 by ~ 92% and at a low temperature of 4°C by ~ 94%.

Conclusions: Given the significance of administering insulin through oral route, deoxycholic acid-modified alginate nanoparticles present a viable option to surmount various obstacles presented by the gastrointestinal.