温度敏感阿霉素脂质体的温度控释特性和稳定性_医学论文.docVIP

温度敏感阿霉素脂质体的温度控释特性和稳定性_医学论文 温度敏感阿霉素脂质体的温度控释特性和稳定性_医学论文 作者：刘同刚　唐敏章　金发光　张生勇　匡永清 【关键词】 阿霉素 关键词: 阿霉素脂质体L-α-二软脂酰磷脂酰胆碱 摘 要:目的 探讨以L-α-二软脂酰磷脂酰胆碱（DPPC）和盐酸阿霉素（ADM）为原料制备的温度敏感阿霉素脂质体（Ts-LADM）的温度控释特性和稳定性. 方法 采用改良逆相蒸发法，以DPPC和ADM为原料制备Ts-LADM，动力学光散射法测定其粒径，以荧光分光光度法检测样本中阿霉素含量，计算包裹率.纯化后的Ts-LADM在不同温度下水浴后经葡聚糖凝胶分离并回收脂质体部分，以酸性乙醇法测定阿霉素的释放量，计算释放率. 结果 Ts-LADM粒径分布范围为0.1～0.43μm，平均粒径0.28μm平均包裹率为37.3%在不同温度下测定的药物释放率分别为:40℃以下小于20%，在DPPC的相变温度附近突然升高，41℃和42℃分别为81.4%和81.6%，44℃时降为77.2%.42℃下延长加热时间药物释放率无明显增加（Pgt0.05）.未经纯化的脂质体于常温下避光贮存5wk，测定其药物包裹率及渗漏率无明显改变（Pgt0.05）. 结论 温度敏感阿霉素脂质体具有良好的温度控释特性和稳定性. 　　Keywords:adriamycinliposomeDPPC Abstract:AIM To explore the thermo-controlled release characteristics and stability of thermo-sensitive liposome of adriamycin（Ts-LADM）prepared with L-α-dipalmitoyl-phos-phatidylcholine（DPPC）and adriamycin（ADM）.METHODS Ts-LADM was made by improved reverse phase evapora-tion（REPE）with DPPC and ADM.The vesicle diameter was determined by dynamic light scattering（DLS）.Encapsu-lation rate was calculated after measurement of ADM in sam-ples through fluorospectrophotometry.The liposome was re-trieved from purified Ts-LADM through sephadex，and the release of ADM was determined by means of acidity ethanol technique.RESULTS The vesicle diameter ranged from0.1μm to0.43μm，with an average of0.28μm，and the average encapsulating rate was37.3%.Measured at different tem-peratures，the ratio of drug release reached the peak around the phase transition temperature of DPPC，which was81.4%at41℃and81.6%at42℃，whereas it was less than20%under40℃and77.2%above44℃respectively，but no fur-ther increase was observed when the temperature was main-tained at42℃（Pgt0.05）.The encapsulation and leakage of unpurified Ts-LADM remained stable（Pgt0.05）when it was stored for5weeks at room temperature and free from light.CONCLUSION Ts-LADM was proved to have good thermo-controlled characteristics and stability. 　　0 引言 　　脂质体的磷脂膜在其相变温度时，可由凝胶态转为液晶态，在磷脂双分子层结构发生改变的过程中，膜的通透性会增加，其内容物漏出增加，作为药物载体而具有温度控制释放的特性.我们以相变温度［1］