郭喆霏,罗永梅,罗宇燕,姜彩云,张永明
GUO Zhefei,LUO Yongmei,LUO Yuyan,JIANG Caiyun,ZHANG Yongming

• 1:中山大学附属第三医院药剂科
• 2:中山大学药学院

摘要(Abstract)：

目的采用SPG膜乳化法制备载牛血清白蛋白的聚乙二醇-聚乳酸聚乙醇酸(PEG-PLGA)微球,研究投药量对微球性质的影响。方法以包封率、载药量及粒径等为指标,评价PEG-PLGA微球的理化性质。采用扫描电镜观察微球的内外形态结构,并考察微球体外释药行为及吸水膨胀性能。结果随着投药量的增加,微球表面及内部孔洞增加,微球释药速率增快。投药量为75 mg时,实际载药量及吸水膨胀有最大值。结论不同投药量所得微球的内外形态在载蛋白PEG-PLGA微球的释放中发挥重要作用。
OBJECTIVE The influence of the theoretical drug loading on the physicochemical properties of the polyethylene glycol-poly lactic acid-co-glycolic acid( PEG-PLGA) microspheres loaded bovine serum albumin( BSA) fabricated by SPG membrane emulsification was investigated. METHODS Encapsulation efficiency,drug loading and particle size were used to evaluate the physicochemical properties of the microspheres. The surface and internal morphology of the microspheres were investigated by scanning electron microscopy. The release behaviors and the swelling of the microspheres were also systematically studied. RESULTS When the theoretical drug loading increased,the number of surface and internal pores increased,resulted in faster drug release. When the dosage was 75 mg,the microspheres showed highest encapsulation efficiency and swelling ratio. CONCLUSION The microspheres prepared with different theoretical drug loading shows different surface and internal morphology,which plays a significant role in in vitro release behaviors.

关键词(KeyWords)： 缓释微球;聚乙二醇-聚乳酸聚乙醇酸;蛋白药物;SPG膜乳化法
sustained-release microspheres;polyethylene glycol-poly lactic acid-co-glycolic acid;protein drug;SPG membrane emulsification

Abstract:

Keywords:

基金项目(Foundation): 广东省医院药学研究基金(2017A18)

作者(Author): 郭喆霏,罗永梅,罗宇燕,姜彩云,张永明
GUO Zhefei,LUO Yongmei,LUO Yuyan,JIANG Caiyun,ZHANG Yongming

参考文献(References)：

• [1]Kazazihyseni F,Landin M,Lathuile A,et al.Computer modeling assisted design of monodisperse PLGA microspheres with controlled porosity affords zero order release of an encapsulated macromolecule for 3 months[J].Pharmaceutical Research,2014,31(10):2844-2856.
• [2]Qi F,Wu J,Hao D,et al.Comparative Studies on the Influences of Primary Emulsion Preparation on Properties of Uniform-Sized Exenatide-Loaded PLGA Microspheres[J].Pharmaceutical Research,2014,31(6):1566-1574.
• [3]Qi F,Wu J,Yang T,et al.Mechanistic studies for monodisperse exenatide-loaded PLGA microspheres prepared by different methods based on SPG membrane emulsification[J].Acta Biomaterialia,2014,10(10):4247-4256.
• [4]郭喆霏,钟晨,罗永梅,等.SPG膜乳化法制备载蛋白的PEG-PLGA复合微球[J].今日药学,2017,27(1):20-23.
• [5]Byeon H J,Kim I,Choi J S,et al.PEGylated apoptotic protein-loaded PLGA microspheres for cancer therapy[J].International Journal of Nanomedicine,2015,10:739-748.
• [6]Liu H,Shi S,Cao J,et al.Preparation and evaluation of a novel bioactive glass/lysozyme/PLGA composite microsphere[J].Drug Development and Industrial Pharmacy,2015,41(3):458-463.
• [7]Patel B,Gupta V,Ahsan F.PEG-PLGA based large porous particles for pulmonary delivery of a highly soluble drug,low molecular weight heparin[J].Journal of Controlled Release,2012,162(2):310-320.
• [8]钟晨,罗宇燕,郭喆霏,等.SPG膜乳化法制备PEG-PLGA微球和PLGA微球载药释药特性的对比研究[J].广东药学院学报,2016,32(3):269-274.
• [9]Zhang K,Tang X,Zhang J,et al.PEG-PLGA copolymers:Their structure and structure-influenced drug delivery applications[J].Journal of Controlled Release,2014,183(1):77-86.
• [10]Tran V T,Karam J P,Garric X,et al.Protein-loaded PLGA-PEGPLGA microspheres:A tool for cell therapy[J].European Journal of Pharmaceutical Sciences,2012,45(1):128-137.
• [11]万斯斯,杨琪,钟晨,等.SPG膜乳化法制备载BSA的PLGA微球的工艺考察[J].广东药学院学报,2016,32(5):550-554.
• [12]黎呐,麦海燕,罗宇燕,等.聚乳酸聚乙醇酸微球冷冻切片方法的研究[J].广东药学院学报,2014,30(1):1-5.
• [13]Gu B,Sun X,Papadimitrakopoulos F,et al.Seeing is believing,PLGA microsphere degradation revealed in PLGA microsphere/PVA hydrogel composites[J].Journal of Controlled Release,2016,228:170-178.
• [14]Dash S,Murthy P N,Nath L,et al.Kinetic modeling on drug release from controlled drug delivery systems[J].Acta Poloniae Pharmaceutica,2010,67(3):217-223.
• [15]Huang X,Li N,Wang D,et al.Quantitative three-dimensional analysis of poly(lactic-co-glycolic acid)microsphere using hard Xray nano-tomography revealed correlation between structural parameters and drug burst release[J].Journal of Pharmaceutical and Biomedical Analysis,2015,112:43-49.
• [16]Mao S,Xu J,Cai C,et al.Effect of WOW process parameters on morphology and burst release of FITC-dextran loaded PLGA microspheres[J].International Journal of Pharmaceutics,2007,334(1):137-148.
• [17]Gasmi H,Danede F,Siepmann J,et al.Does PLGA microparticle swelling control drug release New insight based on single particle swelling studies[J].Journal of Controlled Release,2015,213:120-127.