负载两性霉素B壳聚糖-聚乳酸纳米粒的制备及其释药性能  

Preparation and drug-release property of amphotericin B-loaded chitosan-polylactic acid nanoparticles

作　　者：吴雁[1] 王铁成[1] 李明军[2] 高洪霞[2] 

机构地区：[1]国家纳米科学中心,北京市100019 [2]佳木斯大学附属第一医院,黑龙江省佳木斯市154002

出　　处：《中国组织工程研究与临床康复》2009年第34期6685-6688,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：国家自然科学基金项目资助(90406024)~~

摘　　要：背景:两性霉素B为治疗深部真菌感染的首选药物,但该药无法通过血脑屏障而对隐球菌性脑膜炎的治疗效果甚微。利用纳米粒子作为药物载体的优势,通过相分离透析技术制备负载两性霉素B的壳聚糖-聚乳酸纳米粒子,有望克服两性霉素B的不足。目的:对负载两性霉素B的壳聚糖-聚乳酸纳米粒进行表征,分析其体外药物释放能力。设计、时间及地点:重复测量设计,于2008-11/2009-04在国家纳米科学中心纳米医学与生物实验室完成。材料:壳聚糖,平均相对分子质量为3.4×105,脱乙酰度为93%,为上海卡伯工贸有限公司产品。两性霉素B为Sigma公司产品。方法:在二甲基亚砜溶液中,在三乙胺存在下,通过壳聚糖和D,L-丙交酯的开环聚合反应能够生成壳聚糖-聚乳酸共聚物。该共聚物由亲水壳聚糖段和疏水聚乳酸段组成,在水中能够组装形成纳米粒子。两性霉素B通过相分离透析技术包载于纳米粒子中。主要观察指标:激光粒度分析仪测定纳米颗粒的粒径大小、粒径分布,环境扫描电镜观察纳米颗粒的外观形态,紫外光谱分析负载两性霉素B的壳聚糖-聚乳酸纳米粒的包封率、载药量和释药性能。结果:壳聚糖-聚乳酸纳米粒和负载两性霉素B的壳聚糖-聚乳酸纳米粒,其粒径分别为114nm和153nm(当丙交酯与壳聚糖摩尔比为11∶1时)。纳米粒子粒径分布较窄,呈球形。共聚物中丙交酯与壳聚糖摩尔比影响药物的包封率和载药量,随着丙交酯与壳聚糖摩尔比从11∶1到20∶1,包封率从(62.3±3.5)%增加到(90.7±2.8)%,载药量从(7.8±1.2)%增加到(12.3±1.4)%。随着聚乳酸段质量比增加,纳米粒子尺寸、包封率和载药量增加,而药物释放降低。结论:开环聚合制备壳聚糖-聚乳酸共聚物及用相分离透析方法制备负载两性霉素B纳米粒简便可靠,负载两性霉素B后纳米粒径明显变大,且纳米粒对两性霉素B有很高的包封率,BACKGROUND： Amphotericin B is firstly used to treat deeply fungous infection; however, the therapeutic effect is poor due to inability to cross the blood-brain barrier （BBB）. Chitosan-poty （lactide） （chitosan-co-PLA） copotymer were synthesized by phase separation dialysis technique to overcome the shortage of amphotericin B. OBJECTIVE： To study the representation and drug-release ability of amphotericin B-loaded chitosan-co-PLA nanoparticles. DESIGN, TIME AND SETTING： A repeated measurement design was performed at the Nano-medicine and Nano-biotech Laboratory of National Center for Nanoscience and Technology from November 2008 to April 2009. MATERIALS： Chitosan with the average molecular weight of 3.4× 10^5 and 93% deacetylation degree was produced by KaBo Biochemical Co., Shanghai. Amphotericin B was purchased from Sigma, USA. METHODS： Chitosan-polylactide copolymers were synthesized by ring-opening polymerization of DL-lactide （DLLA） and water soluble chitosan in dimethyl sulfoxide solution in the presence of triethylamine. The chitosan-polylactide copolymers, consisting of hydrophilic chitosan and hydrophobic polylactide segments, could form nanopartictes in water. Amphotericin B was incorporated into chitosan-polylactide polymeric nanoparticles by the phase separation-dialysis method. MAIN OUTCOME MEASURES： Particles size and polydispersity index were detected by laser particle size analyzer. The morphology of amphotericin B-loaded chitosan-polylactide nanoparticles was observed by environmental scanning electron microscopy. In addition, encapsulation capability, loading content and in vitro drug release of the amphotericin B nanoparticles was analyzed by UV-spectrophotometer. RESULTS： The mean diameters of chitosan-polytactide nanoparticles and amphotericin B-loaded nanoparticles were 114 nm and 153 nm （D, L-lactide/chitosan molar ratio 11：1）, respectively. The nanoparticles possessed a uniform particles size distribution and spherical in shape. The entrapment efficiency

关 键 词：两性霉素B 壳聚糖 聚乳酸 纳米粒子 包封率 体外释放 

分 类 号：R318[医药卫生—生物医学工程]