7-乙基-10-羟基喜树碱两亲性嵌段共聚物亚微粒的制备及性质  

Preparation and characterization of 7-ethyl-10-hydroxycamptothecin-loaded hypomicron of amphiphilic block copolymer

作　　者：吴秋澜[1] 栾立标[1] 

机构地区：[1]中国药科大学药剂室,江苏南京210009

出　　处：《药学学报》2007年第4期440-444,共5页Acta Pharmaceutica Sinica

摘　　要：本文用间接法合成了聚乙二醇单甲醚-聚乳酸两亲性嵌段共聚物(methoxypolyethylene glycol-poly lactic acid,PELA),用1HNMR对其结构进行了表征;并以此为载体材料,采用溶解成膜法制备7-乙基-10-羟基喜树碱(7-ethyl-10-hydroxycamptothecin,SN-38)亚微粒,研究共聚物相对分子质量,投药量对亚微粒包封率,载药量及粒径的影响,并考察了该亚微粒的形态及体外释药特性。结果表明,SN-38亚微粒粒径小于200 nm。随着共聚物的相对分子质量增大,载药量与包封率有所下降;随SN-38投药量的增加,载药量和粒径增加,包封率明显降低。透射电镜显示所制备的亚微粒具有核-壳的胶束结构,体外释放实验表明该亚微粒具有明显的缓释效果。本文制备的亚微粒大大增加了SN-38的水溶性,是一种值得研究开发的抗癌药物SN-38的新剂型。Methoxypolyethylene glycol-poly lactic acid （PELA） was synthesized by ring-opening copolymerization of lactide in the presence of mPEG and its structure was characterized by I H NMR. The novel hypomicrons were prepared by solution-casting method using PELA block copolymer as a matrix and 7-ethyl-10-hydroxycamptothecin （SN-38） as an antitumor agent. The morphology, size and size distribution, drug loading, entrapment efficiency, and release characteristics in vitro of the SN-38 loaded hypomicrons were studied. The results showed that the obtained hypomicrons showed spherical shape with the core-shell structure, the sizes are in the range of 157 -238 nm, and the drug loading content varied from 1.35% -3.58% depending on the copolymer composition and the SN-38 fed amount. The in vitro release behavior in phosphate-buffered saline, pH 7.4, exhibited a sustaining release manner and was affected by the copolymer composition. The drug-loaded amount and entrapment efficiency decreased with increasing the molecular weight of the copolymer. With the increasing of the SN-38 fed amount, the drug-loaded amount and the size of hypomicrons increased, the entrapment efficiency decreased. The SN-38 hypomicrons increased the solubility of SN-38 in water and were valuable for the development of the novel dosage form of SN-38.

关 键 词：溶解成膜法 聚乙二醇单甲醚-聚乳酸 亚微粒 7-乙基-10-羟基喜树碱 

分 类 号：R943[医药卫生—药剂学]