Background Glaucoma filtering surgery （GFS） is the most common procedure performed in the treatment of glaucoma.Although antiscarring agents help prevent postsurgical scarring and improve glaucoma surgical outcomes,...Background Glaucoma filtering surgery （GFS） is the most common procedure performed in the treatment of glaucoma.Although antiscarring agents help prevent postsurgical scarring and improve glaucoma surgical outcomes,they may be associated with an increased incidence of severe and potentially blinding complications.Poly（DL-lactide-co-glycolide） （PDLLA/GA） is a bioresorbable polymer,which can be prepared with a large range of physical,mechanical,and biological properties and has been widely used in medicine,including as an absorbable suture and a drug carrier and especially as a scaffold in tissue engineering.This study aimed to evaluate the effect of PDLLA/GA on scar formation after glaucoma filtration surgery （GFS）.Methods Forty-eight New Zealand white rabbits were divided into two groups randomly and GFS was performed on the right eye of each.PDLLA/GA membranes were put under the sclera flap for evaluation.GFS with no membrane inserted served as control.Clinical evaluations of intraocular pressure （lOP） and the presence of a filtration bleb were performed at intervals （3 days,1,2,4,8,12,20,and 24 weeks） postoperatively.At each time point,three eyes per group were excised to observe histological changes such as inflammation and scar formation and the expression of collagen type Ⅳ,proliferating cell nuclear antigen （PCNA）,matrix metalloproteinase-9 （MMP-9）,and tissue inhibitor of metalloproteinase-1 （TIMP-1）.The expression of connective tissue growth factor （CTGF） mRNA was determined by reverse transcription-polymerase chain reaction.Results The lower lOP level and an effective bleb were maintained for a long time after GFS in the PDLLA/GA group.The histological analysis showed less inflammation and scar formation,weaker expression of collagen type Ⅳ and PCNA,more intense MMP-9 and TIMP-1,slightly elevated ratio of MMP-9 and TIMP-1,and a smaller increase in CTGF mRNA postoperatively in the PDLLA/GA group but less than the control group （P ＜0.05）.Conclusion PDLLA/GA 展开更多
When a protein is encapsulated into poly( DL -lactide-co-glycolide)(PLGA) microspheres by means of the double-emulsion method,the harsh microspheres formation process including ultrasonification,exposure to an organic...When a protein is encapsulated into poly( DL -lactide-co-glycolide)(PLGA) microspheres by means of the double-emulsion method,the harsh microspheres formation process including ultrasonification,exposure to an organic solvent and a polymer may cause the denaturation of the protein. In this study,we investigated the enzymatic activity change and the effect of the excipients on the stability of recombinant human Cu,Zn-superoxide dismutase(rhCu,Zn-SOD) during the emulsification. The specific activity recovery was found to be concentration dependent and the excipients involved such as PEG 600 and Tween 20,and trehalose were shown to increase the stability of rhCu,Zn-SOD. The protein structural integrity within the microspheres was analyzed by FTIR. The structure of rhCu,Zn-SOD within PLGA microspheres containing trehalose was found to be similar to that of the native solid state,whereas the protein encapsulated during the preparation in the absence of any excipient changed due to the possible hydrophobic interaction with the polymer. The results suggest that a rational stability strategy for protein to be encapsulated into microspheres should aim at different processes.展开更多
目的建立一种与体内释药数据相关的体外加速释药评价方法，用于胸腺五肽微球的处方优化和质量控制。方法残留法测定微球在大鼠体内的释放情况，绘制体内累积释药曲线；对体外加速释放的重要条件进行筛选，包括释放介质种类、乙醇浓度、...目的建立一种与体内释药数据相关的体外加速释药评价方法，用于胸腺五肽微球的处方优化和质量控制。方法残留法测定微球在大鼠体内的释放情况，绘制体内累积释药曲线；对体外加速释放的重要条件进行筛选，包括释放介质种类、乙醇浓度、表面活性剂浓度、加热温度，进行体内外释放相关性拟合，最大程度模拟体内释放，并采用最终优化的条件验证另两种处方。结果最终优化的体外释放条件为：20%（V/V）乙醇中含0.06%（W/V）Tween 80作为释放介质，程序升温（0～1 h 40°C，1～6 h 45°C，6～30 h 50°C）的方法用于介质加热，（8、13和28）×1033种相对分子质量PLGA制备的微球体外加速曲线与体内释药曲线相关系数r2依次为0.9783、0.9886和0.9780。结论释放介质中加入乙醇并采取程序升温的办法，能最大程度模拟体内释药，可用于胸腺五肽微球的处方优化和质量控制。展开更多
目的探讨优化生长因子微包囊制作方法,观察其释放规律和复合微小颗粒骨异位成骨的效果。方法正交设计优化聚乳酸-羟基乙酸共聚物(poly-DL-lactide-co-glycolide,PLGA)微包囊制作工艺,于2、4、8、12、24、36、48、60、72、84、96、120、...目的探讨优化生长因子微包囊制作方法,观察其释放规律和复合微小颗粒骨异位成骨的效果。方法正交设计优化聚乳酸-羟基乙酸共聚物(poly-DL-lactide-co-glycolide,PLGA)微包囊制作工艺,于2、4、8、12、24、36、48、60、72、84、96、120、144、168、192、216、240和264h计算微包囊的累计释放量。实验取24只Wistar大鼠,随机分为4组(n=6),每只大鼠于双侧股部作1cm切口,制备臀大肌肌袋模型。A组双侧植入胶原,B组双侧植入胶原和颗粒骨,C组双侧植入胶原和重组人骨形成蛋白2(recombinant human bone morphogenetic protein2,rhBMP-2)/PLGA缓释微包囊;D组双侧植入胶原、颗粒骨与rhBMP-2/PLGA缓释微包囊。于术后3、4和5周取样(n=2)行大体和组织学观察。结果各优化变量对微包囊粒径及其包封率均有影响,包囊表面光滑,成球较好。体外能够在11d内缓慢释放。术后3周大体观察,A组未触及移植物,B、C、D组可触及,微包囊呈白色颗粒包裹于组织中。组织学观察:术后3周,A组胶原已经完全吸收,其余3组可见残余胶原;术后4周,A组胶原已不易见到,B组可见微小颗粒骨继续吸收,体积变小;C组包囊体积缩小,囊间成骨性细胞增多;D组微小颗粒骨和微包囊继续吸收,成骨性细胞和软骨性细胞团增多;术后5周,B、C、D组均可见植入物体积减小,包囊被吸收破碎,但颗粒骨和包囊周围的软骨性细胞、成骨性细胞更加密集。结论优化PLGA微包囊制备工艺,使其在体外能够长时间缓释。自体微小颗粒骨可在臀大肌肌袋内异位诱导生成大量成骨性细胞,PLGA微包囊可以与其有机复合,并在减少生长因子用量的同时协同微小颗粒骨成骨。展开更多
文摘Background Glaucoma filtering surgery （GFS） is the most common procedure performed in the treatment of glaucoma.Although antiscarring agents help prevent postsurgical scarring and improve glaucoma surgical outcomes,they may be associated with an increased incidence of severe and potentially blinding complications.Poly（DL-lactide-co-glycolide） （PDLLA/GA） is a bioresorbable polymer,which can be prepared with a large range of physical,mechanical,and biological properties and has been widely used in medicine,including as an absorbable suture and a drug carrier and especially as a scaffold in tissue engineering.This study aimed to evaluate the effect of PDLLA/GA on scar formation after glaucoma filtration surgery （GFS）.Methods Forty-eight New Zealand white rabbits were divided into two groups randomly and GFS was performed on the right eye of each.PDLLA/GA membranes were put under the sclera flap for evaluation.GFS with no membrane inserted served as control.Clinical evaluations of intraocular pressure （lOP） and the presence of a filtration bleb were performed at intervals （3 days,1,2,4,8,12,20,and 24 weeks） postoperatively.At each time point,three eyes per group were excised to observe histological changes such as inflammation and scar formation and the expression of collagen type Ⅳ,proliferating cell nuclear antigen （PCNA）,matrix metalloproteinase-9 （MMP-9）,and tissue inhibitor of metalloproteinase-1 （TIMP-1）.The expression of connective tissue growth factor （CTGF） mRNA was determined by reverse transcription-polymerase chain reaction.Results The lower lOP level and an effective bleb were maintained for a long time after GFS in the PDLLA/GA group.The histological analysis showed less inflammation and scar formation,weaker expression of collagen type Ⅳ and PCNA,more intense MMP-9 and TIMP-1,slightly elevated ratio of MMP-9 and TIMP-1,and a smaller increase in CTGF mRNA postoperatively in the PDLLA/GA group but less than the control group （P ＜0.05）.Conclusion PDLLA/GA
文摘When a protein is encapsulated into poly( DL -lactide-co-glycolide)(PLGA) microspheres by means of the double-emulsion method,the harsh microspheres formation process including ultrasonification,exposure to an organic solvent and a polymer may cause the denaturation of the protein. In this study,we investigated the enzymatic activity change and the effect of the excipients on the stability of recombinant human Cu,Zn-superoxide dismutase(rhCu,Zn-SOD) during the emulsification. The specific activity recovery was found to be concentration dependent and the excipients involved such as PEG 600 and Tween 20,and trehalose were shown to increase the stability of rhCu,Zn-SOD. The protein structural integrity within the microspheres was analyzed by FTIR. The structure of rhCu,Zn-SOD within PLGA microspheres containing trehalose was found to be similar to that of the native solid state,whereas the protein encapsulated during the preparation in the absence of any excipient changed due to the possible hydrophobic interaction with the polymer. The results suggest that a rational stability strategy for protein to be encapsulated into microspheres should aim at different processes.
文摘目的建立一种与体内释药数据相关的体外加速释药评价方法，用于胸腺五肽微球的处方优化和质量控制。方法残留法测定微球在大鼠体内的释放情况，绘制体内累积释药曲线；对体外加速释放的重要条件进行筛选，包括释放介质种类、乙醇浓度、表面活性剂浓度、加热温度，进行体内外释放相关性拟合，最大程度模拟体内释放，并采用最终优化的条件验证另两种处方。结果最终优化的体外释放条件为：20%（V/V）乙醇中含0.06%（W/V）Tween 80作为释放介质，程序升温（0～1 h 40°C，1～6 h 45°C，6～30 h 50°C）的方法用于介质加热，（8、13和28）×1033种相对分子质量PLGA制备的微球体外加速曲线与体内释药曲线相关系数r2依次为0.9783、0.9886和0.9780。结论释放介质中加入乙醇并采取程序升温的办法，能最大程度模拟体内释药，可用于胸腺五肽微球的处方优化和质量控制。
文摘目的探讨优化生长因子微包囊制作方法,观察其释放规律和复合微小颗粒骨异位成骨的效果。方法正交设计优化聚乳酸-羟基乙酸共聚物(poly-DL-lactide-co-glycolide,PLGA)微包囊制作工艺,于2、4、8、12、24、36、48、60、72、84、96、120、144、168、192、216、240和264h计算微包囊的累计释放量。实验取24只Wistar大鼠,随机分为4组(n=6),每只大鼠于双侧股部作1cm切口,制备臀大肌肌袋模型。A组双侧植入胶原,B组双侧植入胶原和颗粒骨,C组双侧植入胶原和重组人骨形成蛋白2(recombinant human bone morphogenetic protein2,rhBMP-2)/PLGA缓释微包囊;D组双侧植入胶原、颗粒骨与rhBMP-2/PLGA缓释微包囊。于术后3、4和5周取样(n=2)行大体和组织学观察。结果各优化变量对微包囊粒径及其包封率均有影响,包囊表面光滑,成球较好。体外能够在11d内缓慢释放。术后3周大体观察,A组未触及移植物,B、C、D组可触及,微包囊呈白色颗粒包裹于组织中。组织学观察:术后3周,A组胶原已经完全吸收,其余3组可见残余胶原;术后4周,A组胶原已不易见到,B组可见微小颗粒骨继续吸收,体积变小;C组包囊体积缩小,囊间成骨性细胞增多;D组微小颗粒骨和微包囊继续吸收,成骨性细胞和软骨性细胞团增多;术后5周,B、C、D组均可见植入物体积减小,包囊被吸收破碎,但颗粒骨和包囊周围的软骨性细胞、成骨性细胞更加密集。结论优化PLGA微包囊制备工艺,使其在体外能够长时间缓释。自体微小颗粒骨可在臀大肌肌袋内异位诱导生成大量成骨性细胞,PLGA微包囊可以与其有机复合,并在减少生长因子用量的同时协同微小颗粒骨成骨。
