背景:蓖麻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,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,并且避免全身毒性的效果.目的:制备可注射可生物降解的聚乳酸羟基乙酸-聚乙二醇-聚乳酸羟基乙酸温敏型凝胶,观察其作为蓖麻毒素缓释载体的体外药物释放行为.设计、时间及地点:对比观察实验,于2007/08-12在福建医科大学医药生物工程中心完成.材料:蓖麻毒素由福建省超声医学研究所纯化,纯度达95%.DL-丙交酯、L-乙交酯由北京元牛融科技有限公司提供.方法:采用开环聚合法合成聚乳酸羟基乙酸-聚乙二醇-聚乳酸羟基乙酸聚合物.主要观察指标:试管翻转法测定相转变温度,高效凝胶渗透色谱法测定相对分子质量,核磁共振推测聚合物嵌段比例,酶联免疫吸附法测定凝胶包载蓖麻毒索的体外释放行为,高效液相色谱法检测释放蓖麻毒素结构完整性,MTT法测定体外释放蓖麻毒素的细胞毒活性.结果:合成的聚合物具有反向热敏性,质量浓度为230g/L时的相转变温度为26℃.聚合物质均分子质量为8 027,数均分子质量为6 643,多元分散系数为1.17,聚乙二醇与聚乳酸嵌段比例约为3:2.载药凝胶在体外持续释放蓖麻毒素达18 d,并且较好地保持了蓖麻毒素结构稳定性和细胞毒活性.结论:合成的聚乳酸羟基乙酸-聚乙二醇-聚乳酸羟基乙酸聚合物是蓖麻毒索较理想的药物缓释载体.%BACKGROUND:Ricin possesses strong cytotoxicity but lacks of specificity.Severe adverse reactions can be caused if ricin is systemically administered.Interstitial chemotherapy with ricin coated by a sustained-release carrier can enhance local therapeutic effects of tumor,avoiding systemic-toxic occurrence.OBJECTIVE:To prepare injectable and biodegradable thermosensitive poly(D,L-lactide-co-glycolide)(PLGA)-polyethylene glycol(PEG)-PLGA copolymer-based hydrogels and to observe the in vitro drug delivery of the PLGA-PEO-PLGA copolymer hydrogel as a sustained-release carrier of ricin.DESIGN,TIME AND SETTING:A controlled observation was performed at the Center for Medical Bioengineering.Fujian Medical University between August and December 2007.MATERlALS:Ricin with a purity of 95%was purified by Fuiian Institute of Ultrasonic Medicine.DL-lactide and L-glycolide were provided by Glycolide Lactide Co.,Ltd..China.METHODS:PLGA-PEG-PLGA-copolymer was synthesized by ring-opening polymerization.MAIN OUTCOME MEASURES:Phase transition temperature was determined by test tube turnover.relativemolecular mass by high-performance gel permeation chromatography,the proportion of block copolymer by nuclear magnetic resonance spectrometry.the in vitro drug delivery of ricin coated by PLGA-PEG-PLGA copolymcr hydrogelby enzyme linked immunosorbent assay.the structural integrity of released ricin by high-performance liquid chromatography,the cytotoxicity of released ricin by methyl thiazolyl tetrazolium assay.RESULTS:The synthesized copolymer PLGA-PEG-PLGA exhibited reverse.thermosensitivity.The phase transition temperature of the copolymer was 26℃at 230 g/L.The weight-average molecular weight and number-average molecular weight of this copolymer was 8 027 and 6 643,respectively,and the multiple-dispersion toefficient was 1.17.The block ratio for PEG and PLGA was 3:2.Drug-loaded PLGA-PEG-PLGA hydrogel could release ricin in vitro for a total of 18 successive days and simultaneously well maintain cytotoxicity and the structural stability of ricin.CONCLUSION:PLGA-PEG-PLGA copolymer is an ideal carrier for sustained delivery of ricin
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