复合万古霉素海藻酸钠/壳聚糖缓释载体的体内释放实验  

In vivo drug releasing test of alginate/chitosan incorporated with vancomycin as a drug delivery system

作　　者：李瑞欣[1] 马小军[2] 王卫明[3] 王为[2] 赵德伟[3] 郭林[3] 于晓光[3] 

机构地区：[1]遵义医学院,贵州省遵义市563003 [2]中国科学院大连化学物理研究所,辽宁省大连市116023 [3]大连大学附属中山医院,辽宁省大连市116001

出　　处：《中国组织工程研究与临床康复》2009年第38期7535-7538,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：大连市科技局青年基金(2004B3SF157);辽宁省自然科学基金(20062135);大连市科技局复合人才基金(2008J21JH001)资助~~

摘　　要：背景:研制一种生物相容性好、可降解、体内释药时间长、来源充分、使用安全的抗生素局部释药系统是目前国内外骨髓炎治疗领域的一个重要发展方向。海藻酸钠和壳聚糖具备优良的生物特性,可以作为抗生素局部释药系统的良好载体。目的:观察海藻酸钠/壳聚糖作为万古霉素缓释载体局部用药的可行性与安全性,并与全身用药比较。设计、时间及地点:体内药物浓度测定,配对分组实验,于2008-08/2009-03在大连大学附属中山医院动物实验室、骨科实验室完成。材料:将海藻酸钠溶液与万古霉素溶液均匀混合后加入CaCO3和柠檬酸钠溶液凝胶化后,利用微胶囊制备仪将上述混合液制备成万古霉素-海藻酸钙凝胶珠。取适量胶珠加入到配好的壳聚糖/万古霉素混合液中反应后收集微胶囊,加醋酸纤维素赋形制备成所需要的载药载体。方法:40只实验兔制作左侧股骨中段局部骨缺损模型,随机分为2组,每组20只。局部用药组于骨缺损中放入一定载药量的复合万古霉素海藻酸钠/壳聚糖缓释载体;全身用药组自兔耳缘静脉注射10%万古霉素(10mg/kg)。主要观察指标:局部用药组术后0.5,1,6,24,72h及1,2周,用高效液相色谱仪检测血清和骨组织中万古霉素浓度。全身用药组注射后10min,0.5,1,6,24,72h测定不同时间点血清、骨组织及肌肉组织中万古霉素浓度。制作局部用药组各重要脏器组织学切片以确定植入物的全身毒性反应。结果:全身用药组24h前各时间点的血药浓度均明显高于局部用药组,24h时全身用药组的血药浓度低于局部用药组;局部用药组的骨骼及肌肉组织药物浓度各时间点均显著超过全身用药组,局部用药组在2周时药物浓度仍然保持较高水平,而全身用药组在持续24h后即出现血药浓度低于最低抑菌浓度的情况。未发现全身毒性的组织学证据。结论:复合万古霉素海藻酸钠/壳�BACKGROUND： An important development orientation of osteomyelitis treating is to prepare a drug delivery system which has the characteristics of excellent biocompatibility, degradable, lengthen drug-released time, source sufficient, as well as use security. Alginate and chitosan can be used as drug delivery system due to the superordinary biological properties. OBJECTIVE： To explore the feasibility and safety of alginate/chitosan incorporated vancomycin （VCM/ACA） as release carrier, in addition, to compare the difference from systematic injection. DESIGN, TIME AND SETTING： An in vivo drug concentration determination, matching grouping experiment. The experiment was performed at the animal and orthopedics laboratories, Affiliated Zhongshan Hospital of Dalian University from August 2008 to March 2009. MATERIALS： The alginate solution and vancocin solution was uniform mixed followed by adding CaCO3 and citrate sodium solution, then the mixed liquor was prepared for vancocin-calcium alginate gel beads with microcapsule preparation instrument. After that, the vancocin-calcium alginate gel beads were reacted with chitosan/vancocin mixed liquor and cellulose acetate to prepare for VCM/ACA release carrier. METHODS： Forty rabbits were prepared for middle of left femur bone defect models, and then randomized divided into 2 groups, with 20 animals in each group. In the local medication group, VCM/ACA release carrier was inlaid to the defects. In the systemic administration group, rabbits were intravenous injected 10% vancocin （10 mg/kg）. MAIN OUTCOME MEASURES： The drug concentrations in the serum and bone tissues of the local medication group was detected by high performance liquid chromatograph at hours 0.5, 1, 6, 24, 72 and weeks 1, 2 after operation. In the systemic administration group, the drug concentrations in the serum, bone and muscle tissues were measured at minute 10 and hours 0.5, 1,6, 24, and 72 after operation. In addition, histological sections of body tissues were prepared to look for sig

关 键 词：海藻酸钠 壳聚糖 万古霉素 药物缓释系统 体内实验 

分 类 号：R318[医药卫生—生物医学工程]