Fabrication and evaluation of pH sensitive chemically cross-linked interpenetrating network [Gelatin/Polyvinylpyrrolidone-co-poly(acrylic acid)] for targeted release of 5-fluorouracil

Abstract

The prime objective of present study was to fabricate novel pH sensitive chemically cross-linked interpenetrating network (IPN) of gelatin/polyvinylpyrrolidone-co-poly (acrylic acid) for controlled delivery of 5-fluorouracil at colon-specific site by combining the properties of natural and synthetic polymers. IPN was prepared through free radical polymerization method by using gelatin and polyvinylpyrrolidone (PVP) as polymers, acrylic acid as monomer and Ethylene glycol dimethacrylate (EGDMA) as a cross-linker. Ammonium peroxodisulphate/sodium hydrogen sulphite were utilized to initiate polymerization process. Series of hydrogels were prepared by altering concentration of gelatin, PVP, acrylic acid and EGDMA. Evaluations with TGA, DSC, XRD, SEM, FTIR and sol–gel analysis were performed to investigate thermal stability, amorphous or crystalline nature, surface morphology and existence of functional groups, which confirm stability and effective cross-linking of hydrogels. Swelling and in vitro drug release studies were performed at both acidic (1.2) and basic (7.4) pH. Hydrogels exhibited higher swelling and drug release at pH 7.4 as compared to at pH 1.2, which confirms the pH sensitive behaviour of fabricated hydrogels. However, it was observed that by increasing polymers, monomer and cross-linker ratios, swelling and drug release of fabricated hydrogels decreases while gel fraction increases. Fabricated hydrogels exhibited biocompatibility with biological system as probed through acute oral toxicity study upon rabbits. Therefore, fabricated IPN could act as a potential controlled drug delivery system for 5-Fluorouracil.