| Objective Preparation of nano hydroxyapatite-calcium sulphate bone repair material containing isoniazid and rifampicin antituberculosis drug,the physical and chemical properties,in vivo and in vitro drug release properties and their biocompatibility evaluation were measured and observed.Methods nHA prepared by chemical precipitation method;by using uniform design,the compressive strength test,select the optimal allocation ratio;the prepared artificial bone at37 ? in SBF degradation,respectively 24 h,72h and 1,2,4,6,8,10,12 W nine time points,artificial observation the degree of degradation of bone surface by scanning electron microscope,measurement of the quality change,the compressive strength were tested by universal testing machine each time point of artificial bone;The artificial bone in 37? PBS in drug release,by HPLC,The release concentration of INH and RFP of 24 h,72h and nine phase points of 24 h,2,4,6,8,10 and 12 W were detected respectively,to observe the drug sustained release performance;artificial bone was implanted into rabbit vertebral body,respectively after 24 h,72h and 1,2,4,6,8,10,12 W nine time points,Determination of the drug content in the surrounding vertebra and paravertebral muscles of the artificial bone,to observe the drug release in vivo.The extraction of artificial bone extracts,using the spectrophotometer to measure and calculate the rate of hemolysis,observe,record and calculate skin primary irritation index,artificial bone embedded in the muscular sac,detected and analyzed in rabbit serum alanine aminotransferase,aspartate aminotransferase,urea nitrogen and creatinine changes,to evaluate its biocompatibility.Results The nHA particles with uniform dispersion and uniform shape were prepared,with a long 150 nm and a needle like or rod like diameter of about 20 nm,when nHA:CSH:INH:RFP=2:8:0.2:0.2 artificial bone can guarantee certain mechanical properties and have certain osteoinduction,its compressive strength is(16.37 + 0.9600)MPa;With the prolongation of immersion time,the surface structure of artificial bone gradually disappeared and the pores decreased.The surface of artificial bone was covered by unstructured degradation products.The quality and compressive strength of artificial bone gradually decreased with the degradation of artificial bone.In vitro release process,the cumulative release percentage of INH 24 h,72h and 1,2,4,6 and 8W phases were 44.58%,71.06%,90.23%,95.98%,98.27%,99.72% and 100%,respectively,while 10 W and 12 W were not detected.The cumulative drug release percentages of RFP at 24 h,72h and 1,2,4,6,8,10 and 12W nine points were 2.70%,16.82%,39.96%,61.71%,61.71%,61.71%,39.96%,16.82%,and 0,respectively.During the release of drug in the artificial bone,the concentration of INH in the vertebral body and paravertebral muscle can be detected at eighth weeks,and there is a sudden release phenomenon.RFP is still in the vertebral body until twelfth weeks of age were detected,and the paraspinal muscles at twelfth weeks is not detected,the overall RFP release is relatively stable,No obvious abrupt release was found.The hemolysis rate of artificial bone was 1.53%,the primary irritation index was 0,There was no significant difference in the results of ALT,AST,BUN and Cr compared with the phase points and the phase points before the implantation.Conclusion The prepared INH loaded RFP nano hydroxyapatite-calcium sulfate artificial bone has good mechanical properties and degradation stability,effective release performance lasts for a long time,has good biocompatibility,It has achieved the design goal of providing structural support and effectively killing Mycobacterium tuberculosis. |
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