Reactive & Functional Polymers, Vol.120, 20-29, 2017
Controlled delivery of oral insulin aspart using pH-responsive alginate/kappa-carrageenan composite hydrogel beads
Diabetes mellitus is a global epidemic currently affecting > 415 million people worldwide. It is a disease caused by either the lack of or a resistance to the insulin, which is a glucose-regulating hormone, in a patient. The low compliance with the subcutaneous administration of insulin by diabetic patients has urged the need for an oral route delivery of insulin. There are two important criteria for an effective oral delivery of insulin, namely the protection of encapsulated insulin from the harsh acidic conditions in the stomach, and the controlled release of insulin at the targeted site of absorption (i.e., the intestine). In this work, the pH-responsive composite hydrogel beads made of the naturally-derived biopolymers (i.e., alginate and kappa-carrageenan) were formed using the extrusion-dripping method. The composite hydrogel beads were tested as the delivery vehicles for insulin aspart. At pH 1.2, the composite hydrogel beads successfully retained the insulin aspart through electrostatic interaction between the positively charged insulin aspart and the negatively charged sulfate groups of the kappa-carrageenan polymers. At pH 7.4, insulin aspart was released in a gradual manner, and the release profile approached zero order kinetic when the concentration of kappa-carrageenan used in the formation of hydrogel bead increased. After incubation of composite hydrogel beads in acidic simulated gastric medium, there was approximately 65% of the insulin aspart remained biologically active in the beads. The results suggest that the alginate/kappa-carrageenan composite hydrogel bead is a promising delivery system for the oral insulin aspart.