PEG-g-(HEMA-co-AA) pH-responsive graft copolymer: A promising approach for the controlled oral delivery of acid-labile rabeprazole sodium.

Abstract

This research presents the development of a novel pH-sensitive PEG (HEMA-co-AA) graft copolymer hydrogel designed to provide controlled and protective delivery of acid-labile drugs, specifically Rabeprazole sodium. The hydrogel was synthesized using polyethylene glycol (PEG), 2-hydroxyethyl methacrylate (HEMA), acrylic acid (AA), with N,N'-methylene bisacrylamide (MBA) as a cross-linker and potassium persulfate (KPS) as an initiator. The hydrogel's structural integrity and formation were confirmed through Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and swelling studies. It is noteworthy that the hydrogel exhibits a different pH-dependent swelling behaviour, which expands under alkaline conditions and maintains its compact structure under acidic conditions. The content of acrylic acid contributed to the high-water retention and the swelling profile indicated that the product was suitable for the specific release of the drug at the site. The in-vitro release of rabeprazole sodium at acidic pH is very low, thus protecting rabeprazole sodium from premature degradation in the stomach; however, controlled release of rabeprazole sodium was achieved at intestinal pH via a non-Fickian diffusion mechanism (Korsmeyer-Peppas n = 0.40-0.62, Higuchi R² = 0.991-0.996) over 12 hours. Moreover, in-vivo acute toxicity studies indicated that the hydrogel is highly biocompatible, suggesting it is safe for use in future therapeutic applications. Overall, the PEG (HEMA-co-AA) hydrogel represents a versatile vehicle for the controlled and local administration of acid-labile pharmaceuticals, thereby promoting increased therapeutic efficacy.