A novel pH-induced thermosensitive hydrogel composed of carboxymethyl chitosan and poloxamer cross-linked by glutaraldehyde for ophthalmic drug delivery.

In this work, a stimuli-responsive three dimensional cross-linked hydrogel system containing carboxymethyl chitosan (CMC) and poloxamer composed of a poly (ethylene oxide)/poly (propylene oxide)/poly (ethylene oxide) (PEO-PPO-PEO) block copolymer was constructed, and its aqueous solution was found to undergo a reversible sol-gel transition upon a temperature and/or pH change at a very low concentration. The hydrogels were synthesized via a cross-linking reaction using glutaraldehyde (GA) as the cross-linking agent. The structures of the hydrogels were characterized by FTIR, XRD, NMR and SEM studies and the swelling behaviour was studied in different buffered solutions. The results obtained indicated that cross-linked F127-CMC underwent discontinuous phase transition in different temperature and pH solutions. The hydrogels at 35°C and pH 7.4 were found to have larger pores than at the other three conditions which resulted in greater swelling. The result of rheological studies showed that the gelation temperature was 32-33°C and the viscosity of the hydrogel increased quickly after gelation. In an addition, the cytotoxicity and in vitro release was studied at different pH values and temperature. The results of a CCK-8 (Cell Counting Kit-8) assay showed that the hydrogel and its physical mixture solution were not cytotoxic to human corneal epithelial cells at a low concentration. Using the drug nepafenac (NP) as a model drug, the controlled drug release behaviour of these hydrogels was investigated. Owing to the formation of F127-CMC/NP retarding the diffusion rate of NP, a sustained release of NP from the hydrogel can be obtained. The release rate was found to be maximum at 35°C and pH 7.4. From these preliminary evaluations, it is possible to conclude that the hydrogels have an excellent potential for application in ophthalmic drug delivery systems.