Novel porous starch/alginate hydrogels for controlled insulin release with dual response to pH and amylase

An important principle in the development of oral insulin is to protect insulin from the harsh conditions of the stomach and release it in a controlled manner in the intestine. In the present study, novel insulin-loaded porous starch-alginate hydrogel systems (In-S-Alg) including In-MS-Alg (prepared with porous maize starch), In-WS-Alg (porous waxy maize starch), and In-RS-Alg (porous rice starch) were successfully developed. As a representative, In-MS-Alg was further coated with gelatinized-retrograded high amylose maize starch (HA) films with different thicknesses to prepare In-MS-HA/Alg hydrogel beads for improving the functionality of controlled release of insulin under the action of α-amylase. The In-S-Alg and In-MS-HA/Alg hydrogel beads were evaluated in terms of structural and morphological properties, encapsulation effect on insulin as well as its release behavior. The results show that insulin was distributed in the pores and cavities of porous starch granules. In In-MS-HA/Alg hydrogel beads, insulin was increasingly blocked inside porous starch with the increased thickness of the HA film. Encapsulation efficiency of insulin in all In-S-Alg and In-MS-HA/Alg hydrogel beads was >80%. Amazingly, both the hydrogel beads successfully achieved the goal of triggered release upon pH changes and α-amylase addition. Most of the insulin (about 90%) was retained in the simulated gastric fluid; while the release rate of insulin in the simulated intestinal fluid increased gradually, and was further accelerated in the presence of α-amylase. Furthermore, for the In-MS-HA/Alg hydrogel beads, the insulin release rate can be gradually reduced by increasing the thickness of the HA film, which provided the possibility to match the rate of increase of the blood glucose level after the intake of food with different glycemic indices. Therefore, the novel hydrogel prepared in this study may be a promising and safe delivery carrier for oral insulin.