万斯斯,赵萍,罗永梅,郭喆霏,罗宇燕,张永明
WAN Sisi,ZHAO Ping,LUO Yongmei,GUO Zhefei,LUO Yuyan,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)：

目的通过一种新的检测方法比较微球释药过程中表面荧光强度的变化,研究聚酯微球的释药机制。方法以异硫氰酸荧光素牛血清白蛋白(FITC-BSA)为模型药物,采用SPG膜乳化法制备聚乳酸-羟基乙酸(PLGA)和m PEG-PLGA微球;以包封率为指标,评价其理化性质;扫描电镜观察微球表面形态;激光共聚焦显微镜(CLSM)观察微球表面荧光强度,并考察微球体外释药行为及降解过程中微球的形态变化。结果 PLGA微球0 d时表面荧光强度较强,微球表面药物分布较多,突释严重,后期微球表面荧光强度均很低,微球表面药物分布少,释放曲线平缓。m PEG-PLGA微球0 d时表面荧光强度较强,微球表面药物分布较多,形成突释,突释后微球表面荧光强度降低,表面药物少,释放进入迟滞期,7 d后微球表面荧光强度增强,表面药物增多,释放加快,30 d时荧光强度降低,药物释放减慢。结论用激光共聚焦显微镜观察微球表面荧光强度的方法可用于研究PLGA微球的释药机制。
OBJECTIVE Elucidating the release mechanism of microspheres by comparing the changes of surface fluorescence during microsphere release. METHODS SPG membrane emulsification method was used to prepare m PEG-PLGA and PLGA microspheres,with FITC-BSA as a model drug. The laser scanning confocal microscope,cold field scanning electron microscope,BCA kit and differential scanning calorimetry were employed to study the in vitro release mechanism of FITC-BSA microspheres. RESULTS Bright fluorescence was observed on the surface of PLGA microspheres at the early stage of the release,and gradually darkened at the later stage of release. m PEG-PLGA microspheres showed typical three-phase release. After the burst release,the fluorescence of the m PEG-PLGA microspheres became darker,and the drug release was accelerated and the fluorescence became bright again when the drug surface was corroded. CONCLUSION The release mechanism of microspheres was successfully characterized by the change of fluorescence intensity of microspheres' surface.

关键词(KeyWords)： 微球释药机制;异硫氰酸荧光素牛血清白蛋白;激光共聚焦显微镜;SPG膜乳化法;表面荧光强度
microsphere's release mechanism;FITC-BSA;CLSM;SPG membrane emulsification;surface fluorescence

Abstract:

Keywords:

基金项目(Foundation): 广东省医院药学研究项目(2015SW12)

作者(Author): 万斯斯,赵萍,罗永梅,郭喆霏,罗宇燕,张永明
WAN Sisi,ZHAO Ping,LUO Yongmei,GUO Zhefei,LUO Yuyan,ZHANG Yongming

参考文献(References)：

• [1]郭喆霏,成晓岚,罗宇燕,等.激光共聚焦显微镜分析载蛋白微球的结构及药物分布[J].中国医院药学杂志,2015,35(15):1381-1384.
• [2]Fredenberg S,Wahlgren M,Reslow M,et al.The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems—A review[J].Int J Pharmaceut,2011,415(1-2):34-52.
• [3]D'Souza S S,Faraj J A,De Luca P P.A model-dependent approach to correlate accelerated with real-time release from biodegradable microspheres[J].Aaps Pharmscitech,2005,6(4):553-564.
• [4]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):268-274.
• [5]罗宇燕,麦海燕,黎呐,等.复乳法及其改良法制备的干扰素PLGA微球载药释药特性的对比[J].中山大学学报(自然科学版),2014,53(3):110-114.
• [6]Qi F,Yang L,Wu J,et al.Microcosmic Mechanism of Dication for Inhibiting Acylation of Acidic Peptide[J].Pharm Res-Dordr,2015,32(7):2310-2317.
• [7]Ye M,Kim S,Park K.Issues in long-term protein delivery using biodegradable microparticles[J].J Control Release,2010,146(2):241-260.
• [8]Dorati R,Genta I,Colonna C,et al.Investigation of the degradation behaviour of poly(ethylene glycol-co-d,l-lactide)copolymer[J].Polym Degrad Stabil,2007,92(9):1660-1668.
• [9]Klose D,Siepmann F,Elkharraz K,et al.How porosity and size affect the drug release mechanisms from PLGA-based microparticles[J].Int J Pharmaceut,2006,314(2):198-206.
• [10]Siepmann J,Elkharraz K,Siepmann F,et al.How Autocatalysis Accelerates Drug Release from PLGA-Based Microparticles:A Quantitative Treatment[J].Biomacromolecules,2005,6(4):2312-2319.
• [11]Faisant N,Siepmann J,Benoit J P.PLGA-based microparticles:elucidation of mechanisms and a new,simple mathematical model quantifying drug release[J].Eur J Pharm SCI,2002,15(4):355-366.
• [12]Gasmi H,Danede F,Siepmann J,et al.Does PLGA microparticle swelling control drug release New insight based on single particle swelling studies[J].J Control Release,2015,213(1):120-127.