Sustained-releasing performance of polymethyl methacrylate bone cement carrying antituberculosis drugs in vitro

doi:10.3969/j.issn.2095-4344.0843

Abstract

Abstract:

BACKGROUND: Antibiotic loaded bone cement has been well studied in clinical prevention and treatment of postoperative infection after artificial joint replacement. However, little is reported on antituberculotic-loaded bone cement.

OBJECTIVE: To investigate the drug release properties of polymethyl methacrylate bone cement carrying antituberculosis drugs in a simulated body fluid (phosphate buffer solution, PBS).

METHODS: The bone cement SimpLex P and antituberculosis drugs, including pyrazinamide, isoniazid, rifapentine, prothionamide, capreomycin, rifampicin, moxifloxacin, and amikacin, were mixed at 40 g:1.5 g and 40 g: 2.5 g ratios to prepare 16 groups of experimental specimens (n=5 per group). In addition, 40 g of bone cement powder was mixed with the liquid monomer to prepare a group of non-loaded bone cement specimens (control group, n=5). Either experimental or control specimens were soaked in PBS simulated body fluid, and then the extractions were taken at different time points to measure concentrations of antituberculosis drugs by high performance liquid chromatography.

RESULTS AND CONCLUSION: The effective sustained-releasing time in the PBS simulated body fluid was 45 and 60 days for 1.5 g and 2.5 g groups of pyrazinamide, was 60 and 45 days for 1.5 g and 2.5 g groups of isoniazid, was 60 and 45 days for 1.5 g and 2.5 g groups of rifapentine, was 150 and 150 days for 1.5 g and 2.5 g groups of protionamide, was 150 and 150 days for 1.5 g and 2.5 g groups of capreomycin, was 45 and 60 days for 1.5 g and 2.5g groups of rifampicin, was 90 and 90 days for 1.5 g and 2.5 g groups of moxifloxacin, and was 60 and 90 days for 1.5 g and 2.5 g groups of amikacin, respectively. All the drug carriers had good drug release characteristics. Especially the 1.5 g and 2.5 g groups of protionamide, 1.5 g and 2.5 g groups of capreomycin, 1.5 g and 2.5 g groups of moxifloxacin and 2.5 g group of amikacin showed a longer period of drug release in accordance with the clinical need. However, our preliminary findings showed that the mechanical strength of the composite bone cement was considerably reduced by isoniazid, rifampicin, rifapentine, or protionamide, while the SimpLex P bone cement carrying pyrazinamide, amikacin, moxifloxacin, or capreomycin showed no changes in the mechanical strength. Therefore, pyrazinamide, amikacin, moxifloxacin, and capreomycin are suitable for the preparation of bone cements carrying antituberculosis drugs.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

Key words: Antitubercular Agents, Tuberculosis, Osteoarticular, Chromatography, High Pressure Liquid, Delayed-Action Preparations, Tissue Engineering

CLC Number:

R318

Yuan Hu-cheng, Shi Shi-yuan, Ma Wen-xin, Yang Xiao-ying, Wang Jia-ming, Wang Zi-li. Sustained-releasing performance of polymethyl methacrylate bone cement carrying antituberculosis drugs in vitro[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(14): 2133-2139.

Figures/Tables 6

References

[1] Zhang YC,Zhang H.One-stage total joint arthropLasty for patients with active tuberculosis.Orthopedics. 2013;36(5):328-330.

[2] Hardinge K,WiLLiams D,Etienne A,et al.Conversion of fusion hips to Low friction arthroplasty.Bone Joint Surg. 1977;59(4):385-392.

[3] Zeng M,Hu Y,Leng Y,et al.Cementless total hip arthroplasty in advanced tuberculosis of the hip.Int Orthop. 2015;39(11): 2103-2107.

[4] 毕红宾,王永清,赵志辉,等.一期病灶清除人工全髋关节置换术治疗活动性髋关节结核[J].中国修复重建外科杂志, 2014,28(8):938-941.

[5] 周胜虎,甄平,沈伟伟,等.晚期活动性髋关节结核全髋关节置换术的临床研究[J].中华关节外科杂志:电子版,2016,10(2):1-6.

[6] 宋向伟,王骞,王自立,等.脊柱结核彻底病灶清除术后3～4.5个月超短程化疗方案的疗效观察[J].中国脊柱脊髓杂志, 2017,27(4): 326-332.

[7] Ge Z,Wang Z,Wei M.Measurement of the concentration of three antituberculosis drugs in thefocus of spinal tuberculosis. Eur Spine J. 2008;17(11):1482-1487．

[8] Oga M,Arizono T,Takasita M,et al.Evaluation of the risk of instrumentation as a foreign body in spinal tuberculosis.Clinical and biologic study.Spine(Phila Pa 1976). 1993;18(13):1890-1894.

[9] 王骞,刘海涛,王自立,等.聚乳酸/聚乙醇酸共聚物涂饰载三联抗结核药人工骨体外释药对比[J].中国组织工程研究, 2017,21(6):911-916.

[10] 王骞,耿广起,丛晓明,等.载三联抗痨药硫酸钙/聚氨基酸缓释材料在兔脊柱结核模型体内的缓释性能[J].中国组织工程研究, 2017,21(10): 1520-1526.

[11] 刘海涛,施建党,王骞,等.硫酸钙/聚氨基酸复合三联抗痨药人工缓释材料的制备及物理性能测定[J].中国矫形外科杂志, 2015,23(21): 1984-1988.

[12] Vora C,Patadia R,MittaL K,et al.Recent patents and advances on anti-tuberculosis drug deLivery and formulations.Recent Pat Drug Devil Formul.2013;7(2):138-149.

[13] BuchhoLz HW,EngeLbrecht H.Depot effects of various antibiotics mixed with PaLacos resins.German Chirurg. 1970;41(11): 511-515.

[14] 刘海涛,施建党,王骞,等.载三联抗结核药物硫酸钙/聚氨基酸人工材料体外缓释性能的观察[J].中国脊柱脊髓杂志, 2015,25(3):239-244.

[15] 马荣,陈振,戈朝晖,等.载异烟肼、利福平白蛋白纳米粒的制备及其体外释药研究[J].第三军医大学学报, 2013,35(21):2336-2339.

[16] 赵晨,王骞,施建党,等.复合三联抗结核药涂层材料(HRZ/PLGA)在大鼠体内释药特性观察[J].中国脊柱脊髓杂志, 2016,26(7):635-641.

[17] 朱荣,龚俊.HPLC测定盐酸莫西沙星的含量和有关物质[J].华西药学杂志, 2017,32(4):398-400.

[18] 王骞,马文鑫.骨关节结核:骨病灶药物分布特点及缓释材料[J].中国组织工程研究,2015,19(48):7859-7859.

[19] 李国华,丁黎明,张斌,等.含抗生素可活动关节骨水泥对全膝关节置换过程中血沉、C反应蛋白及关节功能的影响[J].中国组织工程研究, 2016,20(3):319-323.

[20] 马文鑫,金卫东,王骞,等.载利福平、异烟肼、吡嗪酰胺、莫西沙星骨水泥物理性能及洗脱性能的体外研究[J].中华骨科杂志, 2016,36(11): 735-744.

[21] 李涛,翁习生.抗生素骨水泥在人工关节置换术后感染中应用研究的系统性综述[J].中国矫形外科杂志, 2014,22(20):1868-1874.

[22] 何亮,党晓谦.木糖醇对庆大霉素骨水泥释放及生物力学的影响研究[J].中国现代医学杂志,2014,24(32):9-14.

[23] 虢剑,王骞,马文鑫,等.32例脊柱内固定术后急性感染的临床分析[J].宁夏医科大学学报,2016,38(12):1458-1461.

[24] 马文鑫,王骞,王自立,等.脊柱内固定术后感染的治疗[J].中国矫形外科杂志,2016,24(15):1357-1362.

[25] 施建党,刘园园,王骞,等.病椎固定治疗胸、腰椎结核的疗效分析[J].中华骨科杂志,2016,36(11):681-690.

[26] Jin W,Wang Q,Wang Z,et al.Complete debridement for treatment of thoracolumbar spinal tuberculosis: a clinical curative effect observation.Spine J.2014;14(6):964-970.

[27] 闫军法,王骞,王自立,等.涂饰PLGA载三联抗痨药人工骨的体外释药研究[J].宁夏医科大学学报,2015,37(6):661-664.

[28] 何胤,杨宗强,王骞,等.复合三联抗结核药聚乳酸-羟基乙酸缓释微球的制备及体外释药特性[J].中国脊柱脊髓杂志, 2015,25(5):456-461.