工艺因素对复乳法制备的载牛血清白蛋白PLGA微球形态与释放行为的影响  

Effect of process parameters on morphology and release of protein loaded PLGA microspheres made by W/O/W method

作　　者：金启星[1] 成晓岚[1] 罗宇燕[1] 黄小舟[1] 张永明[1] 

机构地区：[1]中山大学附属第三医院药剂科,广东广州510630

出　　处：《广东药学院学报》2014年第5期539-543,共5页Academic Journal of Guangdong College of Pharmacy

基　　金：广东省重大专项科技计划项目(2011A080504003)

摘　　要：目的研究复乳法的工艺因素对聚乳酸聚乙醇酸(PLGA)微球形态与释放的影响。方法采用复乳法制备载牛血清白蛋白(BSA)的PLGA微球,评价内、外水相体积的变化对微球理化性质的影响;扫描电镜观察微球内外形态,软件计算结构参数;激光共聚焦显微镜观察微球内蛋白的分布情况;考察微球体外释药行为。结果内水相体积增加,微球内外孔洞、截面孔隙率增加,1 d内的突释从12.68%增至56.58%,释药速度加快;通过包裹初乳形成复乳的外水相1(PVA溶液),其体积增加,微球粒径显著增大,平面孔隙率降低,突释从51.58%降低至约15%,释药速度减慢;外水相2(大体积PVA溶液)有促进微球固化的作用,其体积对微球的内外形态及药物分布无显著影响,突释随体积增加略有增加(16.34%至24.28%),释药曲线相似。结论微球内外形态在载蛋白PLGA微球的释放中发挥一定的作用。Objective To study the effect of W/O/W double emulsion method process parameters on microsphere morphology and release.Methods Bovine serum albumin （BSA） poly （lactic-co-glycolic） （PLGA） microspheres were prepared by W/O/W double emulsion method.The effect of the volume of internal and external water phase on the physicochemical properties of microspheres was evaluated,and the scanning electron microscope was taken to observe the outlook and internal morphology of microspheres.The structure parameters were analyzed by the image analysis software,and the confocal laser scanning microscope was utilized to observe protein distribution within the microsphere skeletons.The microspheres in vitro release pattern was studied.Results Increase in internal water phase volume led to increased pores,cross-sectioned porosity,burst release percentage （12.68% to 56.58%） and protein-released rate.By increasing external water phase 1,the particle size changed marginally but burst release decreased from 51.58% to about 15% with lower protein-released rate and cross-sectioned porosity.The volume of external water phase 2 showed no significant influence on microsphere morphology,drug distribution,and proteinreleased pattern,with burst release slightly increased from 16.34% to 24.28%.Conclusion Porosity and internal morphology play a significant role in the release of protein loaded PLGA microspheres.

关 键 词：蛋白微球 聚乳酸聚乙醇酸 内部形态 孔隙率 突释 

分 类 号：R943[医药卫生—药剂学]