Synthesis and characterization of dual responsive sodium alginate-g-acryloyl phenylalanine-poly N-isopropyl acrylamide smart hydrogels for the controlled release of anticancer drug

Abstract

The aim of present study is to design the pH and temperature responsive interpenetrating polymer network (IPN) hydrogels for the controlled release of an anticancer drug, imatinib mesylate. In the course of preparation of these hydrogels, first N-Acryloyl-l-phenylalanine grafted sodium alginate copolymer (NaAla-g-PAPA) was synthesized through free radical polymerization using ammonium persulfate as an initiator. The grafting parameters % grafting, % grafting efficiency, % conversion, % yield, % homopolymer and rate of grafting (Rg) of the reaction were calculated comparatively. The optimum grafting conditions were obtained by alteration of the reaction conditions such as the reaction time, temperature, monomer and initiator concentrations. Then novel dual responsive smart hydrogels were prepared from the graft copolymer (NaAlg-g-PAPA), N-isopropylacrylamide (NIPAM), acrylamide (AAm) by cross linking with N,N′-methylenebisacrylamide (NN-MBA) through free radical polymerization reaction. The hydrogels were characterized by fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) techniques. Various network parameters of hydrogels such as volume fraction in the swollen state (ɸ), the average molecular weight of the polymer chain between two neighboring crosslinks (Mc¯), Flory-Huggins interaction parameter (χ), crosslink density (Ve) and mesh size (ξ) were calculated and explained. Dynamic and equilibrium swelling studies of SAPM hydrgels were performed in distilled water, pH 1.2 and pH 7.4 phosphate buffer solutions. Further, in vitro drug release experiments were conducted in pH 1.2 and pH 7.4 buffer solutions at 25 °C and 37 °C ± 5 °C by taking imatinib mesylate as a test drug. The optimum parameters for maximum % of grafting yield (179) are 240 min of reaction time, 60 °C of reaction temperature, 18.26×10−2 mol/dm3 of APA and 17.54×10−2 mol/dm3 of APS. The in-vitro release studies indicated that the maximum % of IBM release (98 %) was achieved in pH 7.4 buffer at 37 °C within 48 hrs. The swelling data and drug release data were fitted into different empirical kinetic models such as zero order, First order, Higuchi Square root, Hixson-Crowell cube root and Koresmeyer-Peppas equations.