pH-responsive poly(DMAPMA-co-HEMA)-based hydrogels for prolonged release of 5-fluorouracil

This work reports the synthesis and characterization of pH-sensitive hydrogel (PSHs) system composed of N[-3(dimethylamino)propyl] methacrylamide (DMAPMA) and 2-hydroxyethyl methacrylate (HEMA). This hydrogel was prepared efficiently by solution copolymerization method using N,N-methylene bisacrylamide as crosslinker and sodium persulfate/ammonium persulfate as joint initiator system. The chemical structure of the hydrogel was confirmed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. Thermal stability and morphology of the hydrogels were assessed by thermogravimetric analysis and field emission scanning electron microscopy. 5-Fluorouracil (5-FU), an anticancer drug was loaded in the hydrogels to investigate their drug release properties using a human colon cancer cell line (DLD-1). The pH (pH 1.27.4) as well as temperature-sensitive swelling of the hydrogel was also determined. The morphological analysis of the resulting hydrogel revealed a highly interconnected macroporous interior with pore size ranging from 10 to 100 mu m in size. The swelling of the hydrogel was highly influenced by pH of the surrounding medium and higher swelling ratio was observed at simulated intestinal fluid (SIF). The 5-FU release was found to be more efficient in SIF as compared with simulated gastric fluid. The results showed that the 5-FU released from the hydrogel remained biologically active and the developed hydrogel was not cytotoxic. The hydrogel with a 50 : 50 feed ratio of DMAPMA and HEMA was better than the other developed hydrogels. The PSH is furthermore safe for colon-targeted delivery of 5-FU. (c) 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012