A Novel Hydrogel System Based On Chitosan: Preparation And Application In Pharmaceutics

Chitosan, a polysaccharide derived from naturally abundant chitin, gets much attention currently for biomedical application. Hydrogels based on chitosan are attractive systems for drug delivery and tissue engineering, which combine biodegradability and biocompatibility, especially those with the ability to form in situ gel.The present work focuses on a novel gelation system composed of chitosan and NaHCO3, which shows thermal-induced sol-gel transition. The factors that may influence the process of gelation were investigated, such as the NaHCO3 concentration, the temperature and the storage condition. And the gelation mechanism was also discussed and proposed. The gelation time was determined by the vial tilting method. Rheological measurements were carried out to evaluate the storage and loss modulus of both sol and gel. The pH-meter was applied to evaluate the pH value of both sol and gel.The chitosan/NaHCO3 system can exhibit sol-gel transition at the concentration of NaHCO3 ranged from 0.08mol·L-1 to 0.12mol·L-1. Increasing the concentration of NaHCO3 or the environment temperature would speed sol-gel transition of such system, while sol-gel transition would be delayed if the mixture was sealed with wax or sealed under the CO2 atmosphere. The pH value of the gel was higher than that of the corresponding sol, and increased along with the concentration of NaHCO3. It is proposed that the pH value of the system was a key factor to trigger sol-gel transition, which may affect the ionization equilibrium between -NH2 and -NH3+ group in chitosan molecule. As the pH value became higher, more -NH3+ turned to -NH2, then polymer chains entangled to form a three-dimensional network, as a result of the formation of chitosan hydrogel finally.The structure of the gel was investigated by SEM, and its erosion behavior was studied by membrane-free method. The freezing-dried hydrogels showed porous structure. The concentration of NaHCO3 had great influence on the inner morphology of hydrogels, which affected the erosion of the gel.The in situ gelation of this chitosan system was tested in vivo by dorsal subcutaneous injection in rat. Results showed that the gel could form in situ during 3h after injection and maintain morphology in 30 days. The formed chitosan hydrogel was studied as drug carrier, using dipyridamole as the hydrophobic drug and 5-Fluorouracil as the hydrophilic one. In vitro release behavior of the drug-loaded hydrogel coincided with the erosion trend of the corresponding hydrogel, which was influenced by the formulation of gelation system. The amount of drug loaded in the gel also had an impact on the drug release rate, that increasing drug loading would lead to a decrease of the drug release rate.