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万古霉素局部微球注射治疗耐甲氧西林金黄色葡萄球菌感染性椎间盘炎的实验研究 被引量:5

Intra-discal vancomycin-loaded poly lactic acid-glycolic acid microsphere injection for MRSA discitis: an experimental study
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摘要 背景:感染性椎间盘炎的治疗一直是骨科临床的一个难题。目前针对椎间盘炎的治疗均以抗生素应用为基础。局部应用抗生素在预防椎间盘造影术后感染方面已取得了良好的疗效,但单纯抗生素局部注射治疗感染性椎间盘炎需要多次反复穿刺给药,而通过局部注射抗生素缓释制剂可以维持有效的药物浓度并避免相应不良反应。目的目的:采用复乳法制备盐酸万古霉素(VA)聚乳酸-羟基乙酸共聚物(PLGA)载药微球并评估其治疗感染性椎间盘炎的疗效。方法方法:体外评价VA-PLGA微球的粒径分布、形态、包封率、载药量及释放曲线。对耐甲氧西林金黄色葡萄球菌(MRSA)感染椎间盘炎大白兔行VA-PLGA椎间盘内注射治疗,并与VA静脉注射、空白PLGA椎间盘微球注射进行对照,30天后行X线、组织病理学及细菌学检查评价疗效。结果结果:微球粒径在(61.57±4.37)μm^(67.45±8.13)μm之间,包封率(60.20±1.61)%m/m^(75.27±1.60)%m/m,体外释放实验显示其释放时间在30 d以上。体内实验结果表明VA-PLGA局部注射治疗较VA静脉注射治疗炎症反应强度轻(P<0.05),细菌计数明显降低[(1.02×103±1.22×103)CFU/g比(7.51×104±7.16×104)CFU/g,P<0.05]。此外,VA-PLGA局部注射组所用万古霉素仅约20 mg,而VA静脉注射组每只动物所用万古霉素总量约2.4 g,局部注射组仅用静脉注射组1/120的万古霉素剂量即获得了较优的治疗结果。结论结论:局部注射VA-PLGA缓释微球能有效治疗感染性椎间盘炎,在明显降低用药剂量的同时疗效优于静脉注射组。 Background:The treatment of infective discitis has been a tough problem due to the deficiency of blood supply in the inter-vertebral disc. Currently, all the treatments for discitis are based on the application of antibiotics. Application of a certain amount of antibiotics in contrast agents can prevent from post-discography discitis. However, simple antibiotic injection in infected interspace requires repeated puncture administration. Local injection of sustained-released antibiotics can maintain an effective drug concentration for a long time in the injected site and avoid side effects. 〈br〉 Objective:To prepare the vancomycin hydrochloride (VA)-loaded poly lactic acid-glycolic acid (PLGA) copolymer micro-sphere by the multiple emulsion method and evaluate its therapeutic effects on infective discitis. 〈br〉 Methods:Firstly, the particle diameter distribution, shape, encapsulation efficiency, drug-loaded dosage and release curve of VA-PLGA microspheres were evaluated in vitro. Rabbits with methicillin-resistant Staphylococcus aureus infective discitis were treated with VA-PLGA intra-discal injection. Meanwhile, VA intravenous injection and intra-discal injection of blank PLGA microspheres served as controls. Thirty days later, therapeutic effects were evaluated through X-ray radiophotogra-phy, histopathological and bacteriological examination. 〈br〉 Results: Mean particle diameter was between (61.57 &#177; 4.37) μm and (67.45 &#177; 8.13) μm, and mean encapsulation efficiency was between (60.20 &#177; 1.61)%m/m and (75.27 &#177; 1.60)%m/m. In vitro release experiment showed that the release time was over 30 days. The result of in vivo experiment showed that inflammatory reaction in the VA-PLGA intradiscal injection group was milder than the intravenous injection group (P&lt;0.05). The bacterial count was also significantly lower than the intravenous injection group ([1.02&#215;103&#177;1.22&#215;103]CFU/g vs [7.51&#215;104&#177;7.16&#215;10
作者 王飞
出处 《中国骨与关节外科》 2013年第6期519-525,共7页 Chinese Journal of Bone and Joint Surgery
关键词 盐酸万古霉素 缓释微球 椎间盘炎 PLGA Vancomycin hydrochloride PLGA Drug bearing microsphere Discitis
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