| Chitosan is a copolymer of D-glucosamine and Nacetylglucosamine which is a partially N-deacetylated derivative of chitin. Chitosan is a potentially useful pharmaceutical material owing to its good biocompatibility, low toxicity and biodegrability. It has been used in the study of artifical-skin,drug-delivery, artifical vessel, artifical corneal, gene therapy and cancer therapy.In this paper, an injectable thermosensitive in situ gelling hydrogel has been developed. It consists of a chitosan solution neutralized with glycerophosphate (CS/GP) which is liquid at low temperature but gels when heated to 37℃. There are many factors influencing the properties of CS/GP hydrogel.The influences of the concentration of chitosan and glycerophosphate on CS/GP hydrogel have been investigated. Also the influence of the diluted acid, which is used to solve chitosan, on CS/GP hydrogel has been investigated. The CS/GP sol whose concentration of chitosan is 1.8% has the least viscosity, which is beneficial to be injected.1.8% is the optimal concentration of chitosan also because the CS/GP gel with a chitosan concentration of 1.8% has the maximal viscosity. When the concentration of glycerophosphate is 5.6%, the CS/GP sol has the least viscosity while the CS/GP gel has the minimum viscosity. HAc has the best influence on CS/GP hydrogel.The FT-IR results showed difference between CS and CS/GP. In the CS/GP FT-IR spectrum the C=O stretching band appeared at 1630 cm-1 and the O-H and N-H stretching bands appeared at 3700-3100 cm-1 were decreased in comparison to CS. That indicate the occurrence of hydrogen bonding between C=O of chitosan and-OH of glycerophosphate and the junction between -NH of chitosan and-OH of glycerophosphate. It can be concluded that the interactions between chitosan and GP play an important role in the sol-gel transformation of CS/GP.Surface structure and internal structure of all kinds of CS/GP hydrogels were observed by Scanning Electron Microscope. From Scanning Electron Microscope micrographs, we can know that there is a film on the surface of CS/GP hydrogel. The platelike and porous microstructure can be observed inside the CS/GP hydrogel. The Scanning Electron Microscope micrographs clearly illustrate the dependence of hydrogel morphology on the concentrations of CS and GP, and the diluted acid. The pore structures of the resulting gels change from macroporous to microporous with the increase of concentration of CS or GP, and the porous structure becoming more compact and the pore size smaller.This thermosensitive hydrogel is proposed to be used for the sustained release of metronidazole. The in vitro release profiles demonstrated that CS/GP hydrogels show some degree of controlled delivery over metronidazole. The initial release rate of metronidazole from CS/GP hydrogels is very rapid, and the release rate slowed down in the following time. The potential of the hydrogels as vehicles for delivering bovine serum albumin (BSA) were also examined. BSA was trapped during the preparation of CS/GP hydrogel, and its cumulative release behavior in vitro was then investigated. The sustained release effect of hydrogel on BSA is better than that on metronidazole. The release profiles exhibited a fast release rate in the first 12 h, followed by a virtually linear release. It releases 29% in the first 12 hours and 62.8% after 1 week. The BSA released from CS/GP hydrogel has been demonstrated by SDS-PAGE as a single band and their molecular weight was 66.2kD, which is the same as unprossesed BSA. The CS/GP matrix can not only controlled delivery of BSA, but also protect BSA from external environment.Chitosan microspheres (CM) are prepared by the methods of oil/water emulsification. Some properties including SEM, FTIR, bulk density and adsorption performance for BSA are studied. The CMs are smooth-surface and spherical shape of diameter of about 127.761μm. The FTIR spectrum shows the change of the main functional groups on the surface of microspheres.The chitosan microspheres impregnated chitosan/glycerophosphate thermosensitive hydrogels (CS/GP/CM) are achieved by mixing some dried CMs into CS/GP sol and then treated with temperament of 37℃. The gel generation performance of CS/GP/CM is better than that of CS/GP. The viscosity of CS/GP/CM hydrogel is much larger, and it becomes larger obviously with the amount of CMs increase. The BSA release rate reduced with the addition of the CMs. It releases 19.6% in the first 12 hours and 42.43% after 1 week. It is mainly because that the CMs can maintain the stronger gel structure at the same concentration of chitosan and glycerophosphate.
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