【摘要】 [目的]为减少晚期关节结核人工关节置换术后复发风险,探索钛合金材料表面利福平缓释涂层的可行性,并研究其体内外药物释放特性。[方法]通过迈克尔加成反应在钛合金(titanium alloy,Ti alloy)材料表面形成聚多巴胺(poly dopamine,PDA)薄膜;将利福平(rifampicin,RFP)粉剂加载入交联淀粉(crosslinked starches,CS)及四臂巯基聚乙二醇(polyethylene glycol,PEG)中构建水凝胶,通过浸渍-提拉法涂覆于PDA薄膜表面,制成TiPDA-PEG-CS-RFP(Ti-PPCR)涂层。用高效液相色谱法(HPLC)检测Ti-PPCR在模拟体液中药物释放特点;将载药量为6.2 mg的Ti-PPCR钛合金片置入20只新西兰大白兔右侧股骨髁内,分别于术后5、10、15、20 d处死取材,应用HPLC检测术后实验材料周围骨组织、肌肉组织和兔静脉血中RFP释放浓度。[结果]Ti-PPCR在模拟体液中RFP在前3 d释放速率较快,累积释放量占总药量的63.2%,随后释放趋于平缓,总释放率为79.2%,总释放时间达9 d。体内骨组织和肌肉组织中药物浓度迅速上升,到第5 d都达到最高峰,随后平缓降低,总释放周期分别可长达20 d和10 d,且都在最小杀菌浓度以上,静脉血液中未测到利福平。[结论]钛合金表面构建的Ti-PPCR利福平缓释涂层,有一定的利福平局部缓释能力。更多还原

【Abstract】 [Objective] For diminishing the risk of recurrence of joint tuberculosis after arthroplasty,to explore the feasibility of coating on the surface of titanium alloy with sustained-release of rifampicin by observation of the sustained-release properties in vivo and in vitro. [Methods] Poly dopamine(PDA) chemical film was formed on the surface of titanium alloy(Ti alloy) material. Rifampicin(RFP) powder was loaded into crosslinked starches(CS) and polyethylene glycol(PEG) to develop hydrogel.The surface of PDA chemical film was coated with hydrogel by dip-coating method to develop Ti-PDA-PEG-CS-RFP(TiPPCR) composite gel coat. In vitro release kinetics of Ti-PPCR was detected in simulated body fluid(SBF) by high performance liquid chromatography(HPLC). For in vivo detection, 20 New Zealand white rabbits were implanted with a disc-shaped Ti-PPCR plate loaded with 6.2 mg RFP in theright femoral condyle, RFP concentrations in periprosthetic bone and muscle tissues, as well as venous blood were detected by HPLC respectively at 5, 10, 15, 20 days after implantation. [Results] In vitro in SBF, RFP was released rapidlyin the first 3 days which accounted for 63.2% of total load, and then the release tended to be retarded, with a total duration of 9 days and total accumulative releasing rate of 79.2%. In vivo, RFP concentrations of periprosthetic bone and muscle tissues raised rapidly to the peak at 5 days, and then gently reduced, with the total duration of 20 days in bone and 10 days in muscle respectively. Both of the drug levels were above the minimum bactericidal concentration(MBC), although no RFP was detected in the venous blood.[Conclusion] It is feasible to prepare a coating on surface of titanium alloy with sustained-releaseo fRFP.更多还原