Multi-responsive starch-based nanocapsules for colon-targeting delivery of peptides: In vitro and in vivo evaluation.

Colon-targeting delivery of insulin is surging great interests in revolutionizing diabetes. Herein, insulin-loaded starch-based nanocapsules developed by layer-by-layer self-assembly technology were rationally structured. Interactions between starches and the structural changes of the nanocapsules were unraveled to understand in vitro and in vivo insulin release properties. By increasing the deposition layers of starches, the structural compactness of nanocapsules increased and in turn retarded insulin release in the upper gastrointestinal tract. Spherical nanocapsules deposited at least five layers of starches could deliver insulin to the colon in a high efficiency according to the in vitro and in vivo insulin release performance. The underlying mechanism of the insulin colon-targeting release should ascribe to the suitable changes in compactness of the nanocapsules and the interactions between deposited starches after multi-response to the changes in pH, time and enzymes in gastrointestinal tract. Starch molecules interacted with each other much stronger at the intestine than that at the colon, which guaranteed a compact structure in the intestine but a loose structure in the colon for the colon-targeting nanocapsules. It suggested that rather than controlling the deposition layer of the nanocapsules, controlling the interaction between starches could also regulate the structures of the nanocapsules for colon-targeting delivery system.