抗痨药——磁性多孔磷酸三钙陶瓷药物释放系统的实验研究

Experimental study on drug delivery system of antituberculotic-magnetic porous tricalcium phosphate ceramics

目的 研制抗痨药———磁性多孔磷酸三钙 (A MPTCP)药物释放系统 (DDS)。方法将MPTCP及多孔磷酸三钙 (PTCP)浸于抗痨药溶液 ,真空、吸附 ,冻干 ,制得A MPTCP及A PTCP。测定其体外及体内释放抗痨药浓度及持续时间 ,抑菌试验检测其抗结核分枝杆菌作用。结果 A MPTCP体外释放异烟肼达 3 6d以上 ,而A PTCP为 2 4d ;A MPTCP释放有效浓度链霉素达 2 8d ,而A PTCP为 18d。兔股骨中维持异烟肼达 8周以上 ,链霉素达 6周 ;2～ 8周体内取出的A MPTCP对结核分枝杆菌有明显抑制作用。A MPTCP体内有良好的骨传导作用。结论 A MPTCP可望成为治疗骨结核的一种新方法。

Objective To study antituberculotic-magnetic porous tricalcium phosphate (A-MPTCP) ceramics as a possible method for treating bone tuberculosis.Methods The two types of porous ceramic block (MPTCP and PTCP) were placed in a vacuum system into which solution of isoliazid or streptomycin were poured.A vacuum of 500 mmHg was sustained for 30 min,and then the blocks were lyophilized.A-MPTCP blocks were made and A-PTCP blocks used as controls.High performance liquid chromatography (HPLC) was performed to measure its drug concentrations in vitro.After implantation of A-MPTCP in the femur of rabbits,HPLC was performed to measure its drug concentrations in vivo at defined intervals,and then bactericidal ability were shown by antibacterial testing.Results The bactericidal concentration of isoniazid from A-MPTCP was maintained for more than 36 days,but that from A-PTCP decreased to below the detection limit after 24 days.The bactericidal concentration of streptomycin from A-MPTCP was maintained for 28 days,but that from A-PTCP decreased to below the detection limit after 18 days.The in vivo study using rabbit femora showed that an osseous concentration of isoniazid or streptomycin was maintained at 8 weeks or 6 weeks respectively after implantation of A-MPTCP.The antibacterial testing showed that A-MPTCP from the rabbit femora had excellent antimicrobial ability to mycobacterium tuberculosis.Osteoconduction of the A-MPTCP block was good.Conclusion A-MPTCP would be an excellent method to treat bone tuberculosis.