Preparation and characterization of porous starch-based microcapsules loaded with insulin nanoparticles for controllable releasing properties

Oral administration of insulin is still a big challenge due to the harsh gastrointestinal environment. In this study, starch and chitosan were utilized to prepare insulin-loaded microcapsules with controllable releasing properties. Herein, the complexation between chitosan and insulin upon pH adjustment tended to form positively charged insulin nanoparticles (iNPs). At a chitosan/insulin ratio of 1:2, the diameter of iNPs and corresponding insulin loading capacity reached 196.2 nm and 0.70 mg/mg iNPs, respectively. Amylolytic hydrolysis of rice starch granules for 120 min could produce porous rice starch (PRs), enabling the encapsulation of iNPs to form iNPs-loaded PRs (PRs@iNPs). The iNPs were much easier encapsulated by PRs than the free insulin at an equivalent insulin concentration of 0.60 mg/mL. When PRs@iNPs mixed with different concentrations of sodium alginate, the calcium chloride initiated the cross-linking of calcium alginate, and the formation of calcium alginate layer not only protected the starch from the amylase hydrolysis, but also maintained the sustained release of insulin in the simulated gastrointestinal fluid. Moreover, both starch digestion and insulin releasing can be controlled by the concentration of sodium alginate used. This study may provide an efficient benign technology to produce microcapsules loaded with insulin nanoparticles for controllable releasing properties.