万古霉素壳聚糖缓释微球的制备及其体外释药特性和抑菌作用研究
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摘要
目的:制备万古霉素壳聚糖缓释微球,考察其体外释药特性和抑菌作用。方法:采用乳化交联法制备万古霉素壳聚糖缓释微球,观察微球的粒径分布及形态;应用紫外分光光度法测定微球药物含量,计算载药量及包封率;通过体外释放试验,比较其与盐酸万古霉素24 h内的体外释药情况,考察其7 d内的累积释放度(Q);通过体外抑菌试验观察其作用20 d对金黄色葡萄球菌抑菌圈直径的影响。结果:所制万古霉素壳聚糖缓释微球呈圆球形,表面圆整,无明显凹凸和孔隙,平均粒径为(165.6±19.7)μm,平均载药量为(32.6±3.2)%,平均包封率为(53.8±6.3)%,Q_(7d)为82.7%;其与盐酸万古霉素的Q_(2h)分别为18.6%、91.3%;其作用1 d时的抑菌圈直径>3 cm,随其作用时间的延长,抑菌圈直径逐渐缩小。结论:成功制得万古霉素壳聚糖缓释微球,其体外缓释效果明显,且具有良好的体外抑菌作用。
OBJECTIVE:To prepare vancomycin-loaded chitosan sustained-release microspheres and to study its drug release and antibacterial effects in vitro. METHODS:The emulsion cross-linking was used to prepare vancomycin-loaded chitosan sustained-release microspheres,and the particle size and morphology of microspheres were observed. The contents of vancomycin in microspheres was determined by UV spectrophotometry,and drug-loading amount of entrapment efficiency were calculated. Drug release of prepared microspheres and vancomycin hydrochloride within 24 h were compared by release trial in vitro,and then its accumulative release rate(Q)within 7 d was investigated. The effects of prepared microspheres on the diameter of inhibition zone to Staphylococcus aureus after treated for 20 d were observed through in vitro antibacterial test. RESULTS:The microspheres were spherical and complete round without obvious bump and pore. The average particle size of the microspheres was(165.6 ± 19.7)μm;average drug-loading amount was(32.6±3.2)%;average encapsulation efficiency was(53.8±6.3)%;Q_(7 d)was 82.7%. Q_(2 h)of prepared microspheres and vancomycin hydrochloride were 18.6% and 91.3%. The diameter of inhibition zone was higher than 3cm after treated for 1 d,and then decreased gradually as time. CONCLUSIONS:Vancomycin-loaded chitosan sustained-release microspheres can be prepared successfully,and show obvious in vitro sustained-release effect and antibacterial effects.
OBJECTIVE:To prepare vancomycin-loaded chitosan sustained-release microspheres and to study its drug release and antibacterial effects in vitro. METHODS:The emulsion cross-linking was used to prepare vancomycin-loaded chitosan sustained-release microspheres,and the particle size and morphology of microspheres were observed. The contents of vancomycin in microspheres was determined by UV spectrophotometry,and drug-loading amount of entrapment efficiency were calculated. Drug release of prepared microspheres and vancomycin hydrochloride within 24 h were compared by release trial in vitro,and then its accumulative release rate(Q)within 7 d was investigated. The effects of prepared microspheres on the diameter of inhibition zone to Staphylococcus aureus after treated for 20 d were observed through in vitro antibacterial test. RESULTS:The microspheres were spherical and complete round without obvious bump and pore. The average particle size of the microspheres was(165.6 ± 19.7)μm;average drug-loading amount was(32.6±3.2)%;average encapsulation efficiency was(53.8±6.3)%;Q_(7 d)was 82.7%. Q_(2 h)of prepared microspheres and vancomycin hydrochloride were 18.6% and 91.3%. The diameter of inhibition zone was higher than 3cm after treated for 1 d,and then decreased gradually as time. CONCLUSIONS:Vancomycin-loaded chitosan sustained-release microspheres can be prepared successfully,and show obvious in vitro sustained-release effect and antibacterial effects.
引文
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[2]Li X,Ouyang J,Yang H,et al.Chitosan modified halloysite nanotubes as emerging porous microspheres for drug carrier[J].Applied Clay Science,2016,doi:10.1016/j.clay.2016.03.035.
[3]Zhang J,Tang Q,Xu X,et al.Development and evaluation of a novel phytosome-loaded chitosan microsphere system for curcumin delivery[J].International Journal of Pharmaceutics,2013,448(1):168.
[4]冯淑莹,李国明,侯琼,等.金雀异黄素/壳聚糖微球的制备及其释药性能[J].华南师范大学学报:自然科学版,2013,45(5):64.
[5]Doty HA,Leedy MR,Courtney HS,et al.Composite chitosan and calcium sulfate scaffold for dual delivery of vancomycin and recombinant human bone morphogenetic protein-2[J].Journal of Materials Science:Materials in Medicine,2014,25(6):1 449.
[6]Meng D,Dong L,Wen Y,et al.Effects of adding resorbable chitosan microspheres to calcium phosphate cements for bone regeneration[J].Materials Science and Engineering:C,2015,doi:10.1016/j.msec.2014.11.049.
[7]Bitencourt CS,da Silva LB,Pereira PAT,et al.Microspheres prepared with different co-polymers of poly(lactic-glycolic acid)(PLGA)or with chitosan cause distinct effects on macrophages[J].Colloids and Surfaces B:Biointerfaces,2015,doi:10.1016/j.colsurfb.2015.10.011.
[8]Xie M,Zeng L,Zhang Q,et al.Synthesis and adsorption behavior of magnetic microspheres based on chitosan/organic rectorite for low-concentration heavy metal removal[J].Journal of Alloys and Compounds,2015,doi:10.1016/j.jallcom.2015.06.065.
[9]王明波,冯庆玲,等.乳酸-乙醇酸共聚物/壳聚糖复式微球缓释蛋白[J].复合材料学报,2011,28(5):156.
[10]汪小乐,简晓顺,庞廷媛,等.叶酸偶联壳聚糖载多西他赛纳米粒的制备[J].中国药房,2014,25(29):2 740.
[11]Baimark Y,Srisuwan Y.Hollow chitosan microspheres prepared by an oil 1-in-water-in-oil 2 double emulsion method[J].Powder Technology,2013,249(11):436.
[12]Gaspar MC,Sousa JJ S,Pais AA CC,et al.Optimization of levofloxacin-loaded crosslinked chitosan microspheres for inhaled aerosol therapy[J].European Journal of Pharmaceutics and Biopharmaceutics,2015,doi:10.1016/j.ejpb.2015.07.010.
[13]Estevinho BM,Rocha FA,Santos LM,et al.Using water-soluble chitosan for flavour microencapsulation in food industry[J].Journal of Microencapsulation,2013,30(6):571.