载溶菌酶聚乳酸-聚羟基乙酸共聚物微球的形成机制  

Forming mechanism of lysozyme loading polylactic-co-glycolic acid microspheres

作　　者：刘源岗[1] 周长忍[2] 

机构地区：[1]华侨大学材料科学与工程学院,福建省泉州市362021 [2]暨南大学生物材料研究室,广东省广州市510632

出　　处：《中国组织工程研究与临床康复》2007年第31期6198-6202,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：国家科技部重大基础研究项目子课题(G199054306);福建省青年科技人才创新项目(2006F3079);华侨大学高层次人才科研启动金资助项目(06BS215)~~

摘　　要：目的:分析载溶菌酶聚乳酸-聚羟基乙酸共聚物微球的形成机制。方法:实验于2005-03/07在暨南大学生物材料研究室完成。采用双乳液法(W/O/W法)制备聚乳酸-聚羟基乙酸共聚物微球。通过改变微球的制备条件[初乳时间(15,30,45,60,120s)、初乳速度(6000,10000,14000,18000,22000r/min)、聚乙烯醇质量浓度(0,5,25,50,100g/L)、复乳时间(0.5,2.5,5,8,11.5h)、复乳速度(200,400,600,800,1000r/min)、初始药物质量浓度(0,20,40,60,80,100g/L)、内/外水相添加剂(吐温-80、葡聚糖、蔗糖、氯化钠)、油相潜溶剂(丙酮、甲醇、乙醇、二甲基亚砜)],制备不同表面结构和内部结构的聚乳酸-聚羟基乙酸共聚物微球,扫描电镜下观察微球内/外部结构。结果:制备出不同表面结构和内部结构的聚乳酸-聚羟基乙酸共聚物微球。微球表面主要呈3种状态:光滑致密、光滑多孔或粗糙多孔。微球的内部呈多孔洞或核壳结构。①初乳速度较低时(<10000r/min),微球表面以光滑为主,内部多孔,中间有一大的核心;初乳速度较高时(>18000r/min),微球表面较为粗糙,内部孔洞致密,呈蜂巢状。②不同初乳时间制备的微球仍以表面平滑为主,有的微球表面有孔洞,大小在几个微米左右,微球内部仍然是蜂巢状结构。③聚乙烯醇质量浓度影响复乳的稳定性,从而对微球的形成过程影响很大。④复乳时间对微球形成过程的影响较为明显,反应时间过短(<0.5h),微球未充分固化,增加反应时间,球形度相对提高。⑤复乳速度直接影响到复乳体系的稳定。速度较低时(200r/min),形成的微粒体积较大,易形成不规整的大块聚集体。随着搅拌速度的增加,微粒球形度也相应提高。但是当速度过大时(1000r/min),微粒容易破裂形成碎散的不规则聚集体。⑥初始药物质量浓度对微球形成过程的影响很大,药物质量浓度高时(100g/L),微球表面粗糙,碎片较多;药物质量浓度为60g/L�AIM： To investigate the mechanism of forming lysozyme loading polylactic-co-glycolic acid （PLGA） microspheres. METHODS： The experiment was conducted in the Research Laboratory of Biomaterials at Jinan University between March and July in 2005. The PLGA microspheres were prepared by a double-emulsion solvent extraction/evaporation method. Different preparation methods included primary emulsion time （15, 30, 45, 60, 120 seconds）, primary emulsion rate （6 000, 10 000, 14 000, 18 000, 22 000 r/min）, polyvinyl alcohol concentration （0, 5, 25, 50, 100 g/L）, secondary emulsion time （0.5, 2.5, 5, 8, 11.5 hours）, secondary emulsion rate （200, 400, 600, 800, 1 000 r/min）, lysozyme concentration （0, 20, 40, 60, 80, 100 g/L）, ingredient in inner/outer water phase （tween-80, glucan, sucrose, sodium chloride） and sub-reagent in oil phase （acetone, methanol, alcohol, dimethyl sulfoxide）. The inner/outer structure of microspheres was observed through scanning electron microscope. RESULTS： PLGA microspheres with different inner/outer structures were prepared. There were mainly three states of outer surface： smooth and dense surface, smooth and porous surface, rough and porous surface. The inner structure was porous or shell-core.①When primary emulsion rate was below 10 000 r/min, the microspheres were mainly smooth in surface and porous in inner, with a big core, while they presented rough surface with dense pores in comb-like inner when primary emulsion rate was beyond 18 000 r/min.②Microspheres prepared at different primary emulsion times were mostly smooth in surface with occasional pores, while the inner was comb-like. ③Polyvinyl alcohol concentration had great effect on the stability of secondary emulsion system and the formation of microspheres. ④The influence of secondary emulsion time was also obvious. The sphericity degree increased with the time prolonged, ⑤The secondary emulsion rate affected the stability of secondary emulsion system directly. The sphericity degr

关 键 词：溶菌酶 聚乳酸-聚羟基乙酸共聚物微球 形成机制 

分 类 号：R318.08[医药卫生—生物医学工程]