羟基喜树碱纳米微球的制备及体内外释药特性  

The Studies on HCPT/PEG-PBLG Nanosphere:Preparation,Drug Releases and Pharmacokinetic Characteristics

作　　者：王安训[1] 李苏[2] 丁学强[1] 潘仕荣[3] 

机构地区：[1]中山大学附属第一医院口腔颌面外科,广州市510080 [2]中山大学附属肿瘤医院内科 [3]中山大学附属第一医院心内科

出　　处：《中国肿瘤临床》2006年第1期12-15,共4页Chinese Journal of Clinical Oncology

基　　金：广东省科技计划项目资助(编号:2003C50113;2004B30901002)

摘　　要：目的:制备载羟基喜树碱(HCPT)的聚乙二醇-聚谷氨酸苄酯(PEG-PBLG)纳米微球并研究其体外释药特性和体内药代动力学。方法:采用超透析法制备HCPT/PEG-PBLG纳米微球,扫描电镜观察纳米微球的形态,紫外分光光度法观察其体外的释药特性,高效液相色谱法(HPLC)检测并比较HCPT和HCPT/PEG-PBLG纳米微球在兔体内的药代动力学行为。结果:HCPT/PEG-PBLG纳米微球呈核-壳型结构,中间载药库大小约200nm,周围亲水区域厚度约30nm,其载药量和包封率分别为7.5%和56.8%,体内外释药均呈突释-缓释模型。HCPT和HCPT/PEG-PBLG纳米微球的主要药代动力学参数为:t1/2β分别为4.5和10.1h,Cmax分别为2627.8和1513.5μg·L-1,Vd分别为7.3和20.0L,AUC分别为2459.0和2175.9μg·h·L-1。结论:羟基喜树碱纳米微球具有缓释、长循环并增加对组织的亲和性。Objective： To prepare hydroxycamptothecin （HCPT） loaded nanosphere made from poly（ethylene glycol）-poly（γ-benzyl-L-glutamate （PEG-PBLG） and study the drug release characteristic and pharmacokinetic of HCPT/PEG-PBLG nanosphere. Methods： HCPT/PEG-PBLG nanosphere was prepared using super diafiltration method; Scan electron microscope （SEM） was used to observe the shape of nanosphere; The HCPT release characteristic in vitro was evaluated by ultraviolet spectrophotometry. The high-performance liquid chromatography （HPLC） was used to detect and compare the pharmacokinetic parameters of HCPT/PEG-PBLG nanosphere and HCPT in rabbit plasma. Results： The shape of HCPT/PEG-PBLG nanosphere was core-shell structure and the nanosphere＇s size was about 230 nm, with 200 nm in core diameter and 30 nm in shell thickness. The drug loading capacity and drug encapsulation of HCPT/PEG-PBLG nanosphere were 7.5% and 56.8% respectively. The process of HCPT release from nanosphere in vitro and in vivo was composed of two steps, including abrupt-release and sustained-release. The main pharmacokinetic parameters of HCPT and HCPT/PEG- PBLG nanosphere were as follows： the terminal elimination half-life （t1/β） was 4.5 and 10.1 h, the peak concentration （Cmax） was 2627.8 and 1513.51μg·L^-1, the apparent volumn of distribution （Vd） was 7.3 and 20.0 L and the area under the curve （AUC） was 2459.0 and 2175.9 μg·h·L^-1. Conclusion： HCPT/PEG-PBLG nanosphere has the characteristics increased the affinity of HCPT to the tissues.

关 键 词：聚乙二醇 聚谷氨酸苄酯 我药纳米微球 药代动力学 羟基喜树碱 

分 类 号：R94[医药卫生—药剂学]