Development of chitosan/navy bean extract-based nanocarriers for oral delivery of insulin

Strategies have been developed for insulin administration to treat diabetes. In this sense, insulin vehiculation in nanoparticles could effectively protect this bioactive against digestion conditions and allow its intestinal absorption. To exhibit such features, it is essential to choose the materials that will compose the nanoparticles adequately. This study employed genipin-mediated crosslinking of chitosan (CH) and navy bean extract (NBE) to develop nanocarriers, considering their mucoadhesive and cytoadhesive properties, respectively. The effect of different crosslinking reaction conditions on the properties of the nanoparticles was evaluated from a series of experimental designs. Optimized formulations were subjected to in vitro digestion to evaluate insulin delivery. Generally, increasing the CH/NBE ratio formed particles with higher zeta potential. However, insulin added after the crosslinking reaction was less stable under digestive conditions, as it adsorbs onto the nanoparticle surface leading to a decrease in both zeta potential and loading efficiency. The timing of materials addition was also a critical factor influencing the properties of the resulting particles. For instance, when CH or hydrolyzed chitosan is the last ingredient added to the crosslinking reaction, this polysaccharide coats the surface of the nanoparticles, improving its stability in digestion. However, the extent of crosslinking limits insulin release, since only NBE-coated systems release around 15 % of insulin at the intestinal digesta, while those coated with CH or HC showed no release. Therefore, our results provided valuable insights into the most suitable process conditions for the design of nanocarriers for oral insulin delivery.