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三层同轴电喷-去模板法制备核壳纳米颗粒用于蛋白质药物输送

Core-Shell Nanoparticles Fabricated by Tri-capillary Coaxial Electrospray and Template Removal Method for Protein Delivery

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【作者】 曹丽华王红军涂克华蒋宏亮王利群

【Author】 Li-hua Cao;Hong-jun Wang;Ke-hua Tu;Hong-liang Jiang;Li-qun Wang;Department of Polymer Science and Engineering,Zhejiang University;MOE Key Laboratory of Macromolecular Synthesis and Functionalization,Zhejiang University;

【机构】 浙江大学高分子科学与工程学系浙江大学高分子合成与功能构造教育部重点实验室

【摘要】 分别以聚乙二醇(PEG)、聚(丙交酯-乙交酯)(PLGA)和牛血清白蛋白(BSA)为冠、壳和核层材料,采用三层同轴电喷技术制备得到微米颗粒.激光共聚焦显微镜(LSCM)显示,该方法制备得到的微米颗粒呈现核-壳-冠结构.通过脱去该微米颗粒的PEG冠层(模板),得到包载有BSA的纳米颗粒.研究发现,随着壳层PLGA溶液进样速度的减慢,去模板后纳米颗粒的粒径从约146 nm减小到68 nm.BSA在纳米颗粒中的包埋率可高达78.3%,并且其释放没有显著的药物暴释现象.圆二色谱结果表明,同轴电喷过程对BSA二级结构影响很小.因此,利用三层同轴电喷-去模板法可制备得到粒径可调控的蛋白质纳米载体系统,并且该过程中蛋白质的结构基本维持不变.

【Abstract】 A coaxial tri-capillary electrospray and template removal method was proposed to produce nanosized core-shell particles for encapsulating of proteins. Polyethylene glycol( PEG) and poly( D,L-lactide-coglycolide)( PLGA) were used as corona and shell materials,while Bovine serum albumin( BSA),as a model protein,was entrapped in the core. Microparticles with smooth surfaces and distinct core-shell-corona structures were obtained by coaxial tri-capillary electrospray and nanoparticles with diameter about 100 nm were achieved by removing the corona PEG template from core-shell-corona microparticles. Moreover,the nanoparticle size could be modulated by adjusting the feed rate of shell fluid,and the diameter of nanoparticles could be reduced to( 68 ± 8) nm when the shell fluid feed rate was decreased to 0. 5 mL /h. The drug loading content and entrapment efficiency of BSA were 3. 7% and 78. 3%,respectively. It was also found that BSA released from nanoparticles in a typical bi-phased release profile and the process may last for 60 h. The second order structure of BSA released from particles was monitored with circular dichroism spectrum. The results showed that the electrospray process didn’t affect the second order structure of proteins,implying that the denaturation of the protein didn’t occur during the process of electrospraying encapsulation.

【基金】 国家自然科学基金(基金号21174125,21074112)资助项目
  • 【文献出处】 高分子学报 ,Acta Polymerica Sinica , 编辑部邮箱 ,2014年09期
  • 【分类号】TQ460.1;TB383.1
  • 【被引频次】1
  • 【下载频次】156
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