Study On Drug Delivery System Of Ethambutol-Calcium Phosphate Cement-Compound

ObjectiveInvestigate the sustained release characteristics,production as well as the biocompatibility of the Ethambutol-calcium phosphate cement-compound(E-CPC-C), providing experimental basis for clinic.MethodsThe E-CPC-C was made by mixing ethambutol powder with CPC powder inpro to determinate the relationship between E-CPC-C solidification time and content of the EMB.The E-CPC-C(The ratio was 6mg ethambutol to 94mg CPC powder) were implanted into the gluteus maximus or the distal metaphysis of femurs of rabbits, Ethambutol concentration in blood and in tissue around E-CPC-C at different time after implantion was analyzed by mass spectrograph.At the 12th week the pathological examination of the gluteus maximus around E-CPC-C was analyzed to disclose the biocompatibility of E-CPC-C.The E-CPC-C containing 6%EMB were soaked in normal saline,and put in 37℃water bath heater thermostat box,ethambutol concentration in normal saline at different time was analyzed by mass spectrograph to investigate the sustained release characteristics in vitro.Results(1) The clotting time of the E-CPC-C increased with the content of ethambutol, it increased 2.6 minutes when the content of ethambutol was 1%,and increased 17.9-19.7 minutes when the content was 5-6%,increased 26.7minutes when the content was 8%.When the content of ethambutol was 10%,the coagulation status of E-CPC-C should not reach after 72 hours,and the coagulation status should not reach after a week when the content ofethambutol was 12%;(2) E-CPC-C soaked in normal saline can slowly release ethambutol,ethambutol concentration in normal saline decreased after two weeks;(3) Ethambutol concentration in blood of the gluteus grloup was over 0.5μg/ml at the 2^th-7^th day,it reach peak value-1.3μg/ml at the 3^th day, and the femurs group's reached the peak value 0.54μg/ml at the 4^th day,ethambutol concentration in local muscle tissue was 4.12μg/g at the 1^th week,it reduced gradually,was 0.08μg/g at the 12^th week,The ethambutol concentration in local bone tissue was 8.34μg/g at the 1^th week,and was 0.27μg/g at the 12^th week.(4) The pathological section show that there was some inflammation and hyperplasia of granulation tissue in the gluteus maximus around E-CPC-C,and no bone and cartilage tissue.Conclusions(1) There was some relation between The clotting time of the E-CPC-C and the content of ethambutol,the clotting time increased with the content of ethambutol.(2) E-CPC-C can slowly release ethambutol in vivo and in vitro.(3) E-CPC-C was no ossification for the gluteus maximus rabbits.