Study On Preparation Of Injectable Chitosan-based Thermo-Sensitive Hydrogel Loaded With PLGA Microsphere Of Rifampicin

1. to prepare rifampicin microspheres.2.to prepare the Chitosan-β-Glycerophosphate(C-GP) thermo-sensitive hydrogel.3. to prepare the Chitosan-β-Glycerophosphate(C-GP) thermo-sensitive hydrogelas drug carrier to convey the rifampicin microspheres.4. study on the drug release in vito of two kinds of preparations.Methods:1.study on rifampicin,a kind of treatment of tuberculosis and Polylactic-co-glycolic acid(PLGA) were used as carriers to prepare rifampicin microspheres by Emulsification-solvent evaporation method, Simultaneously Ultraviolet(UV) Spectrophotomatry method was used for determination of the drug loading percent, drug entrapment efficiency of RFP-MS. single factor experiments using the drug loading percent,drug entrapment efficiency as evaluating Criterias.because of variance of the theoretical drug loading percent, the optimal formulation was verified by orthogonal design.2. Chitosan andβ-Glycerophosphate were selected to prepare thermo-sensitive hydrogel. Considering the nature of gel time and syringeability,the optimal preparation was adopted.3. to examine administered dose of the rifampicin PLGA microspheres on the hydrogel and decide the dose of the injectable Chitosan-βGlycerophosphate(C-GP) thermo-sensitive hydrogel which loaded the rifampicin PLGA microspheres.4. High-performance liquid chromatography(HPLC) method with UV detector was appiled to detect drug release of the preparation in vitro. Dialysis method was selected to examine the drug release in vitro in pH7.4 phosphatebuffer solution (PBS)(including 1% sodium dodecylsulfate,SDS) as the medium. Analytical methods above were proved to be sensitive and stable.Results:1.the best prescription of the preparation by orthogonal design,prescription assembly was:rifampicin/PLGA=1/5(w/w),PLGA/dichloromethane=1:20(w/w);2%(w/v)of PVA aqueous solution, oil phase/aqueous phase=1:10(v/v), the stirring velocity was 900rpm. RFP-MS prepared with optimal formulation were investigated and evaluated.The photoes Showed that RFP-MS had good appearance, with middle diameter of 42.4238μm,drug loading percent of 17.73%. and entrapment efficiency of 76.55%.2. Considering the nature of gel time and syringeability,the optimal preparation was adopted.the best prescription was:2%(w/v) Chitosan solution of 90% Deacetylation,5%(w/v) ofβ-Glycerophosphate,the hydrogel was owned by mixing two solutions.pH around 7.12 and the optimal thermo-sensitive hydrogel occurred phase transition about 4 minutes.3.study on the dose of the injectable Chitosan-βGlycerophosphatethermo-sensitive hydrogel which loaded the rifampicin PLGA microspheres.2mL hydrogel could load 30mg rifampicin PLGA microspheres. That was maximum dose.4. By the study of drug realease in vito, in the same conditions,RFP-MS release 27.50% and RFP-MS was loaded by hudrogel released 48.3% after 538 hours.the kinetics model Of the two preparation of drug release fitted Higuchi equations.Conclusion:in this paper, Polylactic-co-glycolic acid(PLGA) were used as carriers to prepare rifampicin microspheres and prepare thermo-sensitive hydrogel with Chitosan andβ-Glycerophosphate. for using hydrogel as drug carrier,convey the rifampicin microspheres into joints for in situ gelling injection.this preparation can release for a long time to treat Osteoarticular Tuberculosis and accord with the requirements of injection.