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两性霉素B磁性脂质体的研究

发布时间:2018-04-03 09:40

  本文选题:两性霉素B 切入点:磁性脂质体 出处:《河北科技大学》2014年硕士论文


【摘要】:本课题将抗真菌药物两性霉素B(Amphotericin B,AmB)制成磁性脂质体,旨在对病变部位施加磁场的作用下提高药物浓度,增强磁靶向性,从而降低毒副作用,并对制备的两性霉素B磁性脂质体(AmB magnetic liposomes,AmB-MLPs)进行体内外考察。实验采用薄膜分散加超声的方法制备AmB-MLPs,以粒径和包封率为考察指标,由单因素考察法确定了最优处方和工艺,并对其物理性能进行表征;分别以AmB注射液、AmB-MLPs肺部不加磁场及AmB-MLPs肺部加磁场三种方式经尾静脉注射,对KM小鼠体内的药代动力学、组织分布及肺部靶向性进行考察;用以上三种方式经颈动脉注射,在脑部设置磁场,对AmB进入SD大鼠脑组织提高脑靶向性进行研究。制备的AmB-MLPs的平均粒径为250±12nm,平均包封率为78.02±2.05%,室温下饱和磁化强度为32.54memu·g-1,有良好的体外磁场响应性;KM小鼠药动学结果显示:AmB-MLPs加磁场组比AmB注射液组消除半衰期t1/2β明显延长,清除率CL降低,平均滞留时间MRT延长,,药时曲线下面积AUCt显著增大,说明AmB-MLPs在磁场作用下延长了在血液中的循环时间;AmB-MLPs对肝和脾有一定的被动靶向作用,而在肺部设置磁场时,增强了肺部的磁靶向作用;经颈动脉注射给药,可以在一定程度上提高脑组织的药物浓度,而在脑部施加固定磁场,可以进一步增强药物在脑部的浓集;大鼠脑组织切片普鲁士蓝染色结果显示,脑部加磁场组比不加磁场组可见蓝染颗粒密度大,进一步说明AmB-MLPs经颈动脉注射在磁场作用下,可以进入脑组织,增强了对脑部的磁靶向作用。总之,制备的AmB-MLPs在磁场作用下,可以增强磁靶向性,降低毒副作用。
[Abstract]:In this paper, magnetic liposomes were made from amphotericin amphotericin B(Amphotericin amphotericin. The aim of this study was to increase the concentration of the drug and enhance the magnetic targeting ability under the action of magnetic field on the lesion, so as to reduce the toxicity and side effects.Amphotericin B magnetic liposome Amb magnetic liposome AmB-MLPswas prepared in vitro and in vivo.AmB-MLPswere prepared by thin-film dispersion and ultrasonic method. The particle size and entrapment efficiency were taken as the test indexes. The optimum formulation and process were determined by single-factor method, and the physical properties of the AmB-MLPswere characterized.The pharmacokinetics, tissue distribution and lung targeting of km mice were investigated by injecting AmB injection AmB-MLPs into the lung without magnetic field and AmB-MLPs by the tail vein respectively, and the three methods were injected into the carotid artery by the above three methods, the pharmacokinetics, tissue distribution and lung targeting of km mice were studied.A magnetic field was set up in the brain to study the effect of AmB on brain targeting of SD rats.鍒跺鐨凙mB-MLPs鐨勫钩鍧囩矑寰勪负250卤12nm,骞冲潎鍖呭皝鐜囦负78.02卤2.05%,瀹ゆ俯涓嬮ケ鍜岀鍖栧己搴︿负32.54memu路g-1,鏈夎壇濂界殑浣撳纾佸満鍝嶅簲鎬

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