庆大霉素/壳聚糖局部注射微球给药系统的特性及细胞毒性研究  

Studies on the characteristics and cytotoxicity of gentamicin/chitosan microspheres for local injection

作　　者：庞昌伟[1] 于洪丽[2] 王永红[2] 秦梦[2] 高佃军[1] 张维芬[2] 

机构地区：[1]潍坊医学院,山东潍坊261053 [2]潍坊医学院药学院,山东潍坊261053

出　　处：《中国生化药物杂志》2017年第3期5-9,共5页Chinese Journal of Biochemical Pharmaceutics

基　　金：国家自然科学基金(81573717);国家科技部科技计划项目(2013GA740103);山东省自然科学基金(ZR2012CM025);山东省医药卫生科技发展计划项目(2015WS0057);山东省潍坊市科技计划项目(2014WS045)

摘　　要：目的 构建用于局部注射的庆大霉素/壳聚糖微球给药系统,评价其理化特性及细胞毒性。方法 以庆大霉素为模型药物,壳聚糖为载体,磷脂、羟丙基-β-环糊精为辅料,采用喷雾干燥法制备庆大霉素/壳聚糖/磷脂/羟丙基-β-环糊精局部注射微球,以紫外分光光度法（UV）、扫描电子显微镜（SEM）、X线衍射分析（XRD）、动态膜透析法和四甲基偶氮唑盐法（MTT）等考察微球理化特性及体外细胞毒性。结果 喷雾干燥法成功制备不同药物/载体比例的A、B、C、D、E 5种壳聚糖微球,其产率、载药量、包封率分别为34.38%～46.94%、10.20%～18.67%、61.20%～74.72%,电镜结果显示微球A、B、C成球性差,微球间粘连严重,微球D、E成球形,表面有褶皱,粒径较均匀,粒径在0.5～3μm之间,无粘连;X射线衍射分析结果表明药物已包封在微球中;体外释放结果显示微球D缓释效果较好,24 h累计释放量为83.32%。细胞毒性实验结果表明庆大霉素浓度达到400μg/mL时,微球D的细胞相对增值率仍高于80%,细胞毒性分级为1级,即无细胞毒性。结论 微球D具有良好的理化性质及缓释作用,生物相容性好,有望成为前列腺局部给药的良好载体。Objective To construct the drug delivery system of gentamicin/chitosan microspheres for local injection, and evaluate its physicochemical properties and cell cytotoxicity.Methods Gentamicinwas used as model drug, chitosan as carrier, lecithinand hydroxypropyl-β-cyclodextrin as accessories, and the microspheres of gentamicin/chitosan/lecithin/hydroxypropyl-β-cyclodextrinwas prepared by spray drying method.The physicochemical properties and cell cytotoxicity of themicrospheres were investigated by UV spectrophotometry , scanning electron microscopy, X-ray diffraction, dynamic membrane dialysis and MTT assay.Results Five kinds of chitosan microspheres （ A, B, C, D and E） with different drug/carrier ratios were successfully prepared by spray drying method.The yield, drug loading and entrapment efficiency of the drug-loaded microspheres were 34.38%~46.94%, 10.20% ~18.67%, 61.20% ~74.72%, respectively.SEM results showed that compared with microspheres A, B and C, microspheres D and E own the spherical shape with wrinkled surface and uniform particle size, particle size between 0.5 ~3 μm, no adhesion.X-ray diffraction analysis showed that the drug was encapsulated in the microspheres.The results of in vitro release indicated that microspheres D had a good sustained release effect in the four drug-loaded microspheres.The results of cytotoxicity test showed that when the concentration of gentamicin reached 400 μg/mL, the relative growth rate of microspheres D was still higher than 80% with the cytotoxicity grade was one, ie, no cytotoxicity.Conclusion The microspheres D with good physicochemical properties, sustained-release effect and biocompatibility, is expected to be a good carrier of prostate local drug delivery.

关 键 词：慢性细菌性前列腺炎 局部治疗 庆大霉素 壳聚糖微球 喷雾干燥法 

分 类 号：R78[医药卫生—口腔医学]