Study on the development of nanoparticles based on levan for oral insulin delivery.

Abstract

Oral insulin administration has gained attention as a promising alternative to injections. However, its effectiveness is hindered by the major challenge of degradation by gastric acid. Biopolymer-based nanocarriers have been explored as a solution to address this challenge. This study examines levan, a biopolymer derived fromBacillus licheniformisBK1, for its viability as a nanocarrier for insulin. Levan was modified through acetylation, and both levan (I-Lv) and its acetylated (I-ALv) form were utilized as carriers for insulin in a nanoparticles (NPs) delivery system. The resulting NPs were spherical, with diameters ranging from 250 to 500 nm and encapsulation efficiencies of 78.64% and 88.30%, respectively. The insulin release from I-Lv NPs in simulated gastric fluid exhibited a burst release pattern that was more rapid than that of I-ALv. To further evaluate, the conformational stability of insulin in NPs was analyzed by measuring the transition enthalpy of secondary and tertiary structures. The stability of the secondary structure was determined through alpha-helix content using circular dichroism, while the tertiary structure stability was evaluated via the fluorescence intensity of tryptophan residues. The result revealed that insulin in I-ALv NPs exhibited enhanced conformational stability compared to free-state (FS) insulin and I-Lv NP, with transition enthalpies of 0.91 ± 0.62 and 4.42 ± 0.46 kcal mol^-1for secondary and tertiary structures, respectively. Moreover, preliminaryin vivostudies revealed that I-ALv had a significant impact compared to FS insulin and I-Lv, demonstrating reduction in blood glucose levels. These findings highlight the potential of I-ALv as a promising candidate for antidiabetic therapy and an efficient oral delivery system.