聚乳酸-羟基乙酸包载眼镜蛇毒细胞毒素缓释微球的表征及体外释放行为(英文)  

Superficial property and drug release in vitro of poly lacticoglycolic acid-loaded cytotoxin nanoparticles

作　　者：陈志奎[1] 林礼务[1] 张志强[2] 薛恩生[1] 王艳[1] 俞丽云[1] 

机构地区：[1]福建医科大学附属协和医院超声科,福建省福州市350001 [2]福建医科大学医药生物工程中心,福建省福州市350001

出　　处：《中国组织工程研究与临床康复》2009年第3期575-578,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：背景:眼镜蛇毒细胞毒素具有强烈的细胞毒活性,但缺乏特异性,全身用药可导致严重毒副作用,而采用缓释载体包载进行间质化疗可达到提高肿瘤局部治疗效应,并且减轻全身毒性。目的:制备眼镜蛇毒细胞毒素-聚乳酸-羟基乙酸微球,观察其一般性质和体外释药特性。设计、时间及地点:观察性实验,于2007-12/2008-05在福建医科大学医药生物工程中心完成。材料:聚乳酸-羟基乙酸、聚乙烯醇由中国科学院成都有机化学有限公司提供,广东产中华眼镜蛇毒。方法:采用分子筛、离子交换分离,反相疏水高效液相色谱方法纯化细胞毒素,MTT法检测细胞毒活性,复乳-溶剂挥发法制备载药微球。主要观察指标:扫描电镜观察载药微球的表面形态,激光粒径仪测微球粒径,计算包封率、载药量、体外释放周期。结果:纯化的眼镜蛇细胞毒素具有明显的细胞毒作用,对HepG2细胞12,24h的IC50分别为1.43,1.12mg/L。复乳法制备微球表面光滑圆整,粒径2～8μm,包封率和载药率分别为(74.10±9.92)%和(0.72±0.09)%,21d药物累积释放63.3%,释放细胞毒素保持较好的生物学活性。结论:采用复乳-溶剂挥发法可制备具有较高包封率、良好缓释效果、保持完整生物学活性的眼镜蛇毒细胞毒素-聚乳酸-羟基乙酸微球。BACKGROUND： Cytotoxin （CTX） is characterized by strong cytotoxic activity and absent specificity, of which systemic administration can cause severe toxicity and side effects; however, interstitial chemotherapy may improve therapeutic effect of local tumor and relieve general toxicity using sustained release vector. OBJECTIVE： To prepare cytotoxin/poly lacticoglycolic acid （CTX-PLGA） nanoparticles, and to study the general property and drug release in vitro. DESIGN, TIME AND SETTING： Observational study was performed at Medical Bioengineering Center of Fujian Medical University between December 2007 and May 2008. MATERIALS： Poly lacticoglycolic acid （PLGA） and polyvinyl alcohol were purchased from Chengdu, and CTX was purchased from Guangdong. METHODS： CTX was purified by molecular sieve, ion exchange separation, and reversed-phase high performance liquid chromatography; cytotoxic activity was measured by MTT method; nanoparticles were prepared by multiple emulsion-solvent evaporation technique. MAIN OUTCOME MEASURES： Superficial morphological characteristics were observed using scanning electron microscope, while diameter was measured using laser particle sizing analyzer in order to calculate encapsulation efficiency, drug loading, and release cycle in vitro. RESULTS： Purified CTX had apparent cytotoxic activity, and the IC5o values of HepG2 cells were respectively 1.43 and 1.12 mg/L at 12 and 24 hours. By using multiple emulsion-solvent evaporation technique, the nanoparticles were smooth and intact, diameter 2- 8 μm. The encapsulation efficiency was （74.10±9.92）%, and the drug loading was （0.72±0.09）%. In addition, drug accumulated release was 63.3% at day 21. The released CTX still had a great biologic activity. CONCLUSION： Multiple emulsion-solvent evaporation technique is surely prepared the CTX-PLGA nanoparticles, characterizing by high encapsulation efficiency, great drug release, and entire biologic activity.

关 键 词：细胞毒素 聚乳酸-羟基乙酸微球 缓释 

分 类 号：R318[医药卫生—生物医学工程]