Gelatin-Poly(Ethylene Oxide) Semi-interpenetrating Polymer Network with pH-Sensitive Swelling and Enzyme-Degradable Properties for Oral Drug Delivery

Abstract

The study examined the effect of poly(ethylene oxide) (PEO) molecular weight and concentration in a gelatin-PEO semi-interpenetrating polymer network (semi-IPN) on the swelling behavior and enzyme-induced degradation in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2) at 37°C. Gelatin-PEO semi-IPN with PEO of molecular weight 1,000,000 daltons (1.0 M) at 20% (w/w) concentration had a higher swelling ratio in SGF as compared to SIF. In addition, the pH-sensitive swelling behavior was influenced by the concentration of incorporated PEO of 1.0 M molecular weight in the semi-IPN. The time required for complete hydrogel degradation in pepsin-containing SGF and pancreatin-containing SIF by surface erosion was also dependent on the molecular weight and concentration of PEO. Complete degradation of control gelatin hydrogels in SIF occurred in 2 hr. In contrast, complete degradation of gelatin-PEO semi-IPN in pancreatin-containing SIF occurred in less than 1 hr. Although no difference in riboflavin release kinetics was observed between gelatin and gelatin-PEO hydrogels, there was a marked effect in drug release in the presence of enzymes. In pancreatin-containing SIF, for instance, the total riboflavin load was released in 8 hr from gelatin-PEO semi-IPN. Surface degradation of the hydrogel decreases the diffusional path length of the drug for faster release as the gel degrades. By varying the PEO molecular weight and amount in gelatin-PEO semi-IPN, it is possible to design hydrogels for site-specific oral delivery in the stomach and upper intestine.