Development of inulin nanocarrier for effective oral delivery of insulin: synthesize, optimization, characterization, and biophysical study

The susceptibility of insulin against gastric acid degradation presents a major challenge for oral insulin delivery. The potential of biopolymer-based nanocarriers was investigated in order to address this issue. Inulin, a biopolymer produced by the halophilic bacterium Salinivibrio sp. GM01, has been evaluated for its effectiveness as an insulin nanocarrier. Using central composite design (CCD) method, the optimum condition of inulin-encapsulated insulin (I-In) was achieved at 53 mg of inulin stirred at 17,800 rpm for 10 min, resulting in spherical I-In nanoparticles (I-In NPs) with an average diameter of 416 ± 32 nm and encapsulation efficiency of 87.04 ± 3.01%. The insulin release profile of I-In NPs in simulated gastric fluid follows a burst pattern. Biophysical analysis revealed that insulin in I-In NPs had higher conformational stability than the free state (FS) insulin, as evidenced by an increase in denaturation half-life up to 60 min and the transition enthalpy by 0.29 and 1.53 kcal/mol for secondary and tertiary structures, respectively. Furthermore, preliminary <i>in vivo</i> studies showed that I-In NPs showed significant effect compared to FS insulin for up to 15% in blood glucose level reduction. This study demonstrates the potential of I-In NPs as a promising candidate for antidiabetic therapy and an effective oral delivery system.