药物分子从药物载体中的释放行为与载体的结构有密切关系.本实验中采用丙烯酰胺和丙烯酸等材料,运用水相沉淀的方法,制备了4种不同单体配比的聚丙烯酰胺-丙烯酸(P(Am-co-Ac))共聚物水凝胶.运用红外分析方法对P(Am-co-Ac)组成进行表征....药物分子从药物载体中的释放行为与载体的结构有密切关系.本实验中采用丙烯酰胺和丙烯酸等材料,运用水相沉淀的方法,制备了4种不同单体配比的聚丙烯酰胺-丙烯酸(P(Am-co-Ac))共聚物水凝胶.运用红外分析方法对P(Am-co-Ac)组成进行表征.使用荧光漂白恢复法(FRAP,fluorescence recovery after photobleaching)观察荧光素FITC标记的牛血清白蛋白(BSA)在聚丙烯酰胺-丙烯酸中的扩散行为,并以激光共聚焦显微镜进行实时成像.实验表明,FITC-BSA在不同单体配比的共聚物中的扩散系数是不同的.通过调节聚合物中单体的配比能够达到控制蛋白释放速率的作用,从而为调控蛋白和多肽类药物的缓控释放提供了可能性.展开更多
Purpose: To investigate the effects of topical prazosin and pilocarpine on uveoscleral outflow(Fu) in rabbits.Methods: Sixteen rabbits were randomly divided into the control group (5 rabbits, only topical application ...Purpose: To investigate the effects of topical prazosin and pilocarpine on uveoscleral outflow(Fu) in rabbits.Methods: Sixteen rabbits were randomly divided into the control group (5 rabbits, only topical application of normal saline in the right eye of each rabbit), Prazosin (PZ) treated group (6 rabbits, only 0.1% Prazosin eyedrop 0.1% in the right eye of each one) and Pilocarpine (PC) treated group (5 rabbits, 1% Pilocarpine eye drop in each right eye).Intraocular pressure (IOP)of bilateral eyes of each rabbit was measured before and 1 h after topical application of the eye drop.And the bilateral eyes were perfused with Fluorescein-isothiocyanate bovine serum albumin (FITC-BSA) as the tracer into the anterior chamber of each rabbit for 30 min at 90 min after topical treatment. Then the rabbits were killed for Fu measurement.Results: IOP of PZ-treated eyes decreased [ (0.71 +0.07)kPa ] in 1 hour after PZ application.IOP of PC-treated eyes decreased [(0.70+0.08)kPa] in 1 hour after PC application. The average value of Fu was (0.176+0.048)μl/min in control eyes. The average value of Fu in PZ-treated eyes was (0.339+0.018)μl/min. The average value of Fu in PC-treated eye was(0.123+0.022) μl/min.Conclusion: Both of PZ and PC can decrease IOP in rabbits following topical application.Topical PZ can increase Fu in rabbits and this is one of the mechanisms of PZ-induced IOP decrease.Topical PC can prevent Fu. PC decreases IOP not through uveoscleral pathway.This study demonstrates that uveoscleral pathway plays an important role in aqueous humor drainage. PZ may be a novel drug for decreasing IOP. FITC-BSA is an effective tracer for studying uveoscleral pathway.展开更多
Tissue engineering response may be tailored via controlled,sustained release of active agents from protein-loaded degradable microparticles incorporated directly within three-dimensional(3D)ice-templated collagen scaf...Tissue engineering response may be tailored via controlled,sustained release of active agents from protein-loaded degradable microparticles incorporated directly within three-dimensional(3D)ice-templated collagen scaffolds.However,the effects of covalent crosslinking during scaffold preparation on the availability and release of protein from the incorporated microparticles have not been explored.Here,we load 3D ice-templated collagen scaffolds with controlled additions of poly-(DL-lactide-co-glycolide)microparticles.We probe the effects of subsequent N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide hydrochloride crosslinking on protein release,using microparticles with different internal protein distributions.Fluorescein isothiocyanate labelled bovine serum albumin is used as a model protein drug.The scaffolds display a homogeneous microparticle distribution,and a reduction in pore size and percolation diameter with increased microparticle addition,although these values did not fall below those reported as necessary for cell invasion.The protein distribution within the microparticles,near the surface or more deeply located within the microparticles,was important in determining the release profile and effect of crosslinking,as the surface was affected by the carbodiimide crosslinking reaction applied to the scaffold.Crosslinking of microparticles with a high proportion of protein at the surface caused both a reduction and delay in protein release.Protein located within the bulk of the microparticles,was protected from the crosslinking reaction and no delay in the overall release profile was seen.展开更多
文摘药物分子从药物载体中的释放行为与载体的结构有密切关系.本实验中采用丙烯酰胺和丙烯酸等材料,运用水相沉淀的方法,制备了4种不同单体配比的聚丙烯酰胺-丙烯酸(P(Am-co-Ac))共聚物水凝胶.运用红外分析方法对P(Am-co-Ac)组成进行表征.使用荧光漂白恢复法(FRAP,fluorescence recovery after photobleaching)观察荧光素FITC标记的牛血清白蛋白(BSA)在聚丙烯酰胺-丙烯酸中的扩散行为,并以激光共聚焦显微镜进行实时成像.实验表明,FITC-BSA在不同单体配比的共聚物中的扩散系数是不同的.通过调节聚合物中单体的配比能够达到控制蛋白释放速率的作用,从而为调控蛋白和多肽类药物的缓控释放提供了可能性.
基金This study is supported by Chinese Natural Science Foundation (No.39370724)
文摘Purpose: To investigate the effects of topical prazosin and pilocarpine on uveoscleral outflow(Fu) in rabbits.Methods: Sixteen rabbits were randomly divided into the control group (5 rabbits, only topical application of normal saline in the right eye of each rabbit), Prazosin (PZ) treated group (6 rabbits, only 0.1% Prazosin eyedrop 0.1% in the right eye of each one) and Pilocarpine (PC) treated group (5 rabbits, 1% Pilocarpine eye drop in each right eye).Intraocular pressure (IOP)of bilateral eyes of each rabbit was measured before and 1 h after topical application of the eye drop.And the bilateral eyes were perfused with Fluorescein-isothiocyanate bovine serum albumin (FITC-BSA) as the tracer into the anterior chamber of each rabbit for 30 min at 90 min after topical treatment. Then the rabbits were killed for Fu measurement.Results: IOP of PZ-treated eyes decreased [ (0.71 +0.07)kPa ] in 1 hour after PZ application.IOP of PC-treated eyes decreased [(0.70+0.08)kPa] in 1 hour after PC application. The average value of Fu was (0.176+0.048)μl/min in control eyes. The average value of Fu in PZ-treated eyes was (0.339+0.018)μl/min. The average value of Fu in PC-treated eye was(0.123+0.022) μl/min.Conclusion: Both of PZ and PC can decrease IOP in rabbits following topical application.Topical PZ can increase Fu in rabbits and this is one of the mechanisms of PZ-induced IOP decrease.Topical PC can prevent Fu. PC decreases IOP not through uveoscleral pathway.This study demonstrates that uveoscleral pathway plays an important role in aqueous humor drainage. PZ may be a novel drug for decreasing IOP. FITC-BSA is an effective tracer for studying uveoscleral pathway.
基金the European Research Council[ERC Advanced Grant 3205983D-E]the Medical Research Council,Arthritis Research UK,Reumafonds and the UKRMP。
文摘Tissue engineering response may be tailored via controlled,sustained release of active agents from protein-loaded degradable microparticles incorporated directly within three-dimensional(3D)ice-templated collagen scaffolds.However,the effects of covalent crosslinking during scaffold preparation on the availability and release of protein from the incorporated microparticles have not been explored.Here,we load 3D ice-templated collagen scaffolds with controlled additions of poly-(DL-lactide-co-glycolide)microparticles.We probe the effects of subsequent N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide hydrochloride crosslinking on protein release,using microparticles with different internal protein distributions.Fluorescein isothiocyanate labelled bovine serum albumin is used as a model protein drug.The scaffolds display a homogeneous microparticle distribution,and a reduction in pore size and percolation diameter with increased microparticle addition,although these values did not fall below those reported as necessary for cell invasion.The protein distribution within the microparticles,near the surface or more deeply located within the microparticles,was important in determining the release profile and effect of crosslinking,as the surface was affected by the carbodiimide crosslinking reaction applied to the scaffold.Crosslinking of microparticles with a high proportion of protein at the surface caused both a reduction and delay in protein release.Protein located within the bulk of the microparticles,was protected from the crosslinking reaction and no delay in the overall release profile was seen.
