透析法制备载羟基喜树碱-聚乳酸纳米粒及其理化性质研究  

Preparation and Characteristic of Hydroxycamptothecin-loaded PLA Nanoparticles Using Dialysis Method

作　　者：罗颖[1] 李乐[2] 王衍戈[2] 常迪[2] 侯振清[2] 张其清[2,3,4] 

机构地区：[1]厦门大学医学院 [2]厦门大学材料学院,福建省生物医学工程重点实验室,福建厦门361005 [3]中国医学科学院,北京协和医学院,北京100730 [4]天津市生物医学材料重点实验室,天津300192

出　　处：《厦门大学学报（自然科学版）》2010年第6期832-837,共6页Journal of Xiamen University：Natural Science

基　　金：国家科技支撑计划(2007BAD07B05);厦门市科技计划项目(3502Z20093009)

摘　　要：采用直接透析法制备载羟基喜树碱-聚乳酸(HCPT-PLA)纳米粒并研究其理化性质、体外释放和细胞毒性.以HCPT-PLA纳米粒的载药率为评价标准,通过正交设计考察PLA浓度、HCPT与PLA的质量比和不同截留分子质量透析袋对其指标的影响.利用Malvern nano-zs粒度测定仪、XRD、DSC和激光共聚焦显微镜(CLSM)对HCPT-PLA纳米粒的理化性质进行表征.薄膜透析法考察体外释药特性;MTT试验检测细胞毒作用.在优化条件下制备的载药纳米粒为实心球形,平均粒径为226.8 nm,多分散系数为0.270,载药率为7.49%.HCPT是以晶体状态均匀分布于PLA纳米粒中.药物体外释药符合Higuchi方程Q=2.000 6X1/2-2.593 4,r=0.989 2.MTT试验显示HCPT-PLA纳米粒呈现明显细胞毒作用.透析法制备HCPT-PLA纳米粒,粒径小且分布均匀,具有较好的缓释特性;细胞毒性试验表明HCPT-PLA纳米粒具有较强的抑瘤作用且抑瘤效果优于HCPT.In this paper,HCPT-loaded PLA nanoparticles of desired size range for treating liver cancer were successfully prepared by using the facile dialysis method without the additional surfactants.Effect of experimental parameters on preparation of HCPT-loaded PLA nanoparticles was evaluated.The results of orthogonal test showd that the mass ratio of HCPT to PLA was the most important determinant of drug-loaded content.The obtained HCPT-loaded PLA nanoparticles had spherical shape and smooth surface with a mean diameter of about 226.8 nm.The distribution of HCPT in PLA nanoparticles was uniform and HCPT was a crystalline state existed in PLA nanoparticles.In vitro release study indicated that HCPT in PLA nanoparticles showed a sustained release trend over a period of 30 days with no burst release at initial stage.The mean in vitro cumulative release percentage of HCPT from HCPT-loaded PLA nanoparticles vs time curve fit well with the Higuchi equation（Q=2.000 6X1/2-2.593 4,r=0.989 2）.Cytotoxicity assay against BEL-7402 show that,compared to HCPT,the HCPT-loaded PLA nanoparticles have higher cytotoxicity.

关 键 词：羟基喜树碱 聚乳酸纳米粒 体外释放 细胞毒性试验 

分 类 号：R944.9[医药卫生—药剂学]