Research Of Insulin-loading PH-sensitive Hydrogel Microspheres

pH-sensitive hydrogels was a novel drug carrier, which could automatically sense thechanges of the pH values in the body. And then it would shrink or swell to realizesite-specific release and intelligent administration. This topic prepared two pH-sensitivehydrogel microspheres by suspension polymerization and inverse suspensionpolymerization. The factors such as monomer, crosslinking agent, initiator, dispersant,dispersion medium were investigated in the preparation of the study. The optimum recipeof hydrogel microspheres with good particle size distribution and swelling ratio wasdetermined. The morphology and internal structures of hydrogel microspheres wereobserved with scanning electron microscope (SEM), and the polymerization finish wassuccessful fabrication were confirmed via Fourier transform infrared spectroscopy (FTIR).Bovine serum albumin (BSA) as a model drug, in vitro release studies of the twopH-sensitive hydrogel microspheres showed a significant pH-sensitivity. BSA release wasless than20%under acidic conditions (pH1.2), whereas under the alkaline conditions (pH6.8) it was quickly into balance (more than90%). P(AA-g-PEGMA) hydrogelmicrospheres were chosen for the insulin in vitro release study. Under acidic conditions(pH1.2) insulin release was also less than20%, whereas under the alkaline conditions (pH6.8) insulin released quickly and achieved to balance (more than90%). The cytotoxicitytest of hydrogel microspheres was conducted by culturing Caco-2cells. Differentconcentrations of hydrogel microspheres co-cultured with Caco-2cells. The cell survivalrates were all close to100%, which indicating that the hydrogel microspheres had nocytotoxicity. Caco-2cell monolayer preincubated in Transwell unit was used to simulateintestinal epithelial cells. The insulin permeability from Caco-2cell monolayer showedthat the hydrogel microspheres promoted the absorption of insulin. The cell experimentsshowed that the hydrogel microspheres were suitable as an oral insulin carrier. In vivostudies, Wistar male rats were established as the diabetic animal model. The comparativestudy was conducted among oral insulin hydrogel microspheres with subcutaneous insulinsolutions and oral insulin solutions. The results showed that oral insulin hydrogelmicrospheres had hypoglycemic effects and the released insulin was absorb of theintestinal epithelial cells. These results all indicated that the pH sensitive hydrogelmicrospheres as oral durg delivery carriers of macromolecular protein drug had potentialresearch value and application prospect.