There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscope (FESEM). The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA) and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU) from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA), and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug delivery carriers.
AbstractN-succinyl chitosan (NSC) remains a promising chitosan derivative to develop targeted drug delivery, wound dressings, and tissue engineering systems. All these systems are important in life sciences. NSC is an amphiprotic derivative obtained from the N-acylation of chitosan. NSC exhibits extraordinary biocompatibility, significantly increased aqueous solubility in acidic and basic media without affecting the biological properties, appreciable transfection efficiency, and the ability to stimulate osteogenesis. NSC shows enhanced bioavailability, which highlights its potential applications in the biomedical field. This review briefly introduces chitosan, including its limitations as a biomaterial, and modifications of chitosan with a particular focus on acylation, along with a comprehensive overview of the synthesis, characterization, properties, biodistribution, and toxicological/biopharmaceutical profile of NSC. Furthermore, it extensively surveys current state-of-the-art NSC-based formulations for drug delivery with special emphasis on protein delivery, anti-cancer activity in the colon, as well as nasal and ophthalmic targeted gene/drug delivery. Moreover, it discusses NSC-based biomaterial applications in articular, adipose, and bone tissue engineering. In addition, it describes recent contributions of NSC-based hydrogels in wound dressings along with a brief account of drug delivery in combination with tissue engineering. Finally, it presents potential current challenges and future perspectives of NSC-based formulations in the biomedical field.
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