Smart gelation of chitosan solution in the presence of NaHCO₃ for injectable drug delivery system

In situ gelling systems are attractive as injectable vehicles for drug delivery. The present work described a novel gelation process of acidic chitosan solution in the presence of sodium bicarbonate (NaHCO₃). The NaHCO₃ concentration played an important role in this gelling system. When it came within the appropriate range, the chitosan/NaHCO₃ system would stay at sol state in certain condition and showed sol–gel transition from the top to the bottom after heating. The rheological properties of the gelling system, as well as the morphology and erosion behavior of the formed chitosan hydrogels were evaluated as a function of the NaHCO₃ concentration in sols. The hydrogels showed porous morphologies with some diversification depending on the NaHCO₃ concentration, which also affected their erosion behaviors and drug release rates. Moreover, the gelation mechanism of such chitosan/NaHCO₃ system was studied and proposed as the formation of three-dimensional chitosan network with physical junctions thanks to the deprotonation of –NH₃ ⁺ in chitosan accompanying with the gradual neutralization between HCO₃ ⁻ and acid. In vivo gelation test was also performed by the dorsal subcutaneous injection of chitosan/NaHCO₃ solution in rat. The formation of in situ gels suggested such system promising applications in injectable drug delivery system.