Physico-chemical characterization of pH-sensitive N-Succinyl chitosan-g-poly (acrylamide-co-acrylic acid) hydrogels and in vitro drug release studies

摘要

Since last decade, momentous development has been made in the biomedical field. However, the contribution of polymer hydrogels as drug delivery carrier cannot be ignored. Crosslinking of natural and synthetic polymer has established promising characteristics in stimuli sensitive hydrogels for targeted drug delivery application. In this work, we synthesized N-succinyl chitosan and characterized via Fourier transform infrared (FTIR) spectroscopy, Nuclear magnetic resonance (NMR) spectroscopy, X-ray diffrac-tion (XRD), and differential scanning calorimetry (DSC). Then, we synthesized N-succinyl chitosan-g-Poly (acrylamide-co-acrylic acid) hydrogel via chemical crosslinking of N-succinyl chitosan, acrylamide and acrylic acid. Crosslinking was performed using free radical mechanism. Here, N, N-methyl-enebisacrylamide (MBA) and ammonium persulfate (APS) were used as crosslinking agent and initiator, respectively. The hydrogels were synthesized by varying the concentration of monomers, initiator, and crosslinking agent. The chemical interactions in the synthesized hydrogel network were evaluated by FTIR, XRD, and DSC. Field emission scanning electron microscope (FESEM) showed porous morphology of hydrogels. The yield %, gel contents, and gel time were thoroughly examined and excellent results were found. The rheology study was performed to measure the mechanical strength. Moreover, swelling study revealed that hydrogels were highly swellable and depended on the various concentrations of initiator, monomers, and crosslinking agent. The results also showed that pH, type and concentration of salt so-lutions have strong influence on the swelling properties. Hydrogels expressed reversible swelling behavior in buffer solutions and buffer and salt solutions. Furthermore, theophylline was encapsulated during the synthesis of hydrogel and encapsulation efficiency was found in the range of 59-83%. In addition, theophylline release was observed in buffer solutions of pH 1.2 and pH 7.4. The results revealed the significant effect of pH and hydrogel composition on drug release. The theophylline release was found in the range of 14-24% in buffer solution pH 1.2 and 67-93% in buffer solution pH 7.4. The drug release data showed good fitting to Ritger- Peppas model and release kinetics followed non-Fickian anomalous transport mechanism and relaxation of polymers (case Ⅱ transport). It was also observed that theophylline maintained its chemical activity after in vitro release. According to the observed facts, synthesized hydrogels can be adapted for their prospective exploitation in targeted drug delivery applications.