Study On Preparation And Characteristics Of Chitosan-Cyclodextrin Inclusion Complex Thermosensitive Hydrogel

Hydrogels are composed of three-dimensional polymer networks that have a highnumber of hydrophilic groups. Fully swollen hydrogels are soft, pliable, and lowinterfacial tension with water or biological fluids. The high water content of hydrogelsrenders them compatible with most living tissue and their viscoelastic natureminimizes damage to the surrounding tissue when implanted in the host. Theseproperties make hydrogels ideal candidate in biomedical applications such as remedyinjuries to living systems. In recent years, hydrogels made of chitosan andglycerophosphate are going to be one of the best hydrogels because of theirthermosensitive, superordinary biocompatibility and mechanical property. Butchitosan-based hydrogels are hydrophilic and mainly uesd in hydrophilic drugs, whichlimits their application. This research introduces inclusion complex of β-cyclodextrininto chitosan-based hydrogel, expecting to resolve the extant problem.Methods:1. Prepared aspirin-β-cyclodextrin inclusion complex by saturated solutionmethod. Optimized the clathration condition using design export software, anddetected the embedding rate, infrared spectrum of the inclusion complex. In vitrorelease of aspirin form inclusion complex was also investigated.2. Prepared chitosan-β-cyclodextrin hydrogel and chitosan-inclusion complexhydrogel, explored the optimal condition of preparation. Detected the temperaturesensitivity, turbidity, infrared spectrum, surface morphology and in vitro release of thehydrogel.3. Detected the pharmacodynamics and biocompatibility of hydrogel.Results:1. The optimal clathration condition to prepare Aspirin-β-cyclodextrin inclusioncomplex was that the molar ratio of β-cyclodextrin to Asp was0.82, clathrationtemperature was49℃, and clathration time was2hours. The embedding rate could be up to61.19%. The formation of the bonding between–COOH group of Aspirin and O-H group of β-cyclodextrin might play an important role in the process of clathrationaccording to infrared spectrum. Results of in vitro release showed that the drug releasefrom matrix occurred through Fickian diffusion mechanism. The cumulative release ofaspirin reached only40%over24h, indicating that the drug inclusion complex couldrelease slowly.2. The optimal conditions for the preparation of the thermosensitive hydrogelwas that the concentration of chitosan was1.5%(w/v), the ratio of chitosan/β-cyclodextrin was1/1or2/1(w/w) and the ratio of chitosan/αβ-glycerol phosphatewas9/1(v/v). The hydrogel could transformed from sol into gel at37℃in10minutesand hydrogel prepared under this condition showed good transparency. Infraredspectrum showed that the C=O and N-H of chitosan connected with–OH of αβ-glycerol phosphate and formed hydrogel. The cumulative release of aspirin fromchitosan-β-cyclodextrin hydrogel reached60%over36h, and that from chitosan-inclusion complex hydrogel reached less than35%during the same time.3. The investigation of pharmacodynamics showed that the chitosan-β-cyclodextrin hydrogel loaded with aspirin had equivalent effect of analgesia andantiinflammatory comparing with free aspirin. Forthermore, the effectiveness wasmore duration than the free Aspirin. The result of in vitro hemolysis experimentdemonstrated the chitosan-β-cyclodextrin hydrogel possessed satisfactoryhemocompatibility. Interstitial implanted to the mice showed that the chitosan-β-cyclodextrin hydrogel had satisfactory biocompatibility and had no harm on thefunction of liver and kidney. So the hydrogel could be potentially used as a safe,delayed release targeted drug carrier.