表面修饰二氧化硅的脂质体对阿霉素的包埋与释放性质(英文)

Encapsulation and release of doxorubicin from silica-coated liposome

背景:脂质体药物载体近年来被用以增加药物的稳定性,提高药效,降低药物的毒副作用。然而研究发现由于稳定性较差,脂质体药物载体难以实现药物缓释与长效给药。大量研究表明,二氧化硅无毒,具有化学惰性和生物相容性,是很好的修饰材料。目的:为了提高脂质体药物载体的稳定性,延长给药时间,采用二氧化硅对脂质体进行表面修饰并用于抗癌药物盐酸阿霉素的包埋。设计、时间及地点:体外观察实验,于2007-05/2008-06在哈尔滨工业大学生物医学工程中心的纳米医药与生物传感器实验室完成。材料:L-α-二棕榈酰磷酯酰胆碱购自南京康森特化工有限公司,正硅酸乙酯购自美国Aldrich公司,盐酸阿霉素购自北京华奉联博科技有限公司,葡聚糖凝胶G-50购自瑞典Amersham公司,其他化学试剂均为分析纯。方法:通过溶胶-凝胶沉积二氧化硅的方法修饰模板L-α-二棕榈酰磷酯酰胆碱脂质体。主要观察指标:通过激光粒度仪与Zeta电位仪测定二氧化硅修饰后的脂质体粒径分布与表面电荷;通过透射电镜观察二氧化硅修饰后脂质体的形态;通过傅里叶变换红外光谱表征材料的化学结构;通过荧光光谱仪测定溶液中阿霉素浓度;通过阿霉素浓度回归方程计算脂质体药物包封率与脂质体体外释放速率。结果:①成功制备了二氧化硅包裹修饰的脂质体。②傅里叶变换红外光谱结果显示在1166cm-1,1080cm-1,859cm-1和526cm-1存在Si-O-Si振动峰。③二氧化硅修饰的脂质体对阿霉素的包封率为72.4%。④药物体外释放结果显示二氧化硅包裹修饰的脂质体使阿霉素达到缓释效果。结论:由于在脂质体的表面形成纳米级厚度的无机Si-O-Si网络作为保护层,使得脂质体的稳定性显著提高,并且对阿霉素有缓释效果。

BACKGROUND： For decades, liposome drug carrier has been used to enhance drug stability and efficacy, reduce drug toxicity and adverse effects. However, they fail to provide long-term delivery due to insufficient stability. Studies have demonstrated that silica is not toxic, with chemically inert and biological compatibility, and can be used as modified material. OBJECTIVE： To characterize the silica coated liposome and investigate the controlled release property. DESIGN, TIME AND SETTING： In vitro observation. The study was performed at the Nanomedicine and Biosensor Laboratory, Biomedical Engineering Center, Harbin Institute of Technology from May 2007 to June 2008. MATERIALS： Dipalmitoylphosphatidylcholine （DPPC） was purchased from Nanjing Kangsente Chemical Engineering Company; tetraethylorthosilicate （TEOS） was purchased from Aldrich, USA. Doxorubicin （DOX） was purchased from Beijing Huafeng United Technology Company; Sephadex G-50 was purchased from Amersham Biosciences, Sweden. All other chemical agents were of analytical purity. METHODS： Liposome was formed from DPPC following the precipitation of silica by sol-gel method. MAIN OUTCOME MEASURES： Zeta-potential and dynamic light scanning were used for zeta-potential measurement and particle size distribution; transmission electron microscopy was used to collect the image of particle morphology; Fourier transform infrared spectroscopy （FTIR） was used to display chemical characteristics of Si-O-Si structure; Spectrophotofluorimetry was used to determine DOX regression equation and was further used for calculation in drug encapsulation efficiency and in vitro release. RESULTS： （1）Silica coated liposome was successfully prepared. （2）FTIR proofed the presence of Si-O-Si at 1 166, 1 080, 859 and 526 cm-1. （3）The DOX encapsulated silica coated liposome had encapsulation efficiency of 72.4%. （4）Drug release profiles showed that sustained release of DOX was achieved after modification of silica on liposome. CONCLUSION： With Si-O-Si as protective layer, the liposome has increased stability and prolonged drug release.