Poly(vinyl alcohol)/poly(hydroxypropyl methacrylate-co-methacrylic acid) as pH-sensitive semi-IPN hydrogels for oral insulin delivery: preparation and characterization

Abstract

A series of pH-sensitive semi-interpenetrating polymer network (semi-IPN) hydrogels poly(vinyl alcohol)/poly(hydroxypropyl methacrylate-co-methacrylic acid) (PVA/P(HPMA-co-MAA)) were synthesized by free-radical polymerization of HPMA and MAA in the presence of PVA. The physicochemical property of the obtained hydrogels was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analyses and scanning electron microscopy (SEM) measurements. The SEM photograph revealed the network formation with uniform pore distribution. The swelling behavior of each hydrogel in buffer solution showed a simultaneous sensitivity to pH and ionic strength: the swelling ratio of all hydrogels was higher in neutral environment than in acidic medium; besides, equilibrium swelling ratio of the hydrogels decreases as the ionic strength increases. Insulin was loaded into the PVA/P(HPMA-co-MAA) semi-IPN hydrogel. The in vitro insulin release experiment was carried out in buffer solutions at pHs 1.2 and 6.8. Results showed that the release of entrapped insulin was inhibited at pH 1.2 but obviously increased at pH 6.8. Cell viability revealed that the hydrogels were biocompatible. After oral administration of insulin-loaded hydrogel to streptozotocin-induced diabetic rats at 75 IU/kg, a sustained reduction in blood glucose level was observed. Therefore, the semi-IPN PVA/P(HPMA-co-MAA) hydrogels are potential vehicles for oral delivery of protein drugs.