Biodegradable, pH-Responsive Carboxymethyl Cellulose/Poly(Acrylic Acid) Hydrogels for Oral Insulin Delivery

Biodegradable and pH-responsive carboxymethyl cellulose/poly(acrylic acid) hybrid hydrogels are synthesized. The hydrogels deswell in acidic artificial gastric fluid (AGF) but rapidly swell in neutral artificial intestinal fluid (AIF), rendering selective enzymatic degradation of the gels as well as accelerated drug release from insulin-loaded hydrogels in AIF. Oral administration of insulin-loaded hydrogels to streptozotocin-induced diabetic rats leads to a continuous decline in the fasting blood glucose level within 6h post-administration, and the relative pharmacological availability increases more than 10 times compared to oral administration of free insulin solution. The relative bioavailability of hydrogel-encapsulated insulin after oral administration to healthy rabbits is 6.6%.