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The sustained releasing ability of CEL-PLGA-MS in vitro and its inhibitory effects on experimental choroidal neovascularization after intravitreal injection / 中华实验眼科杂志
Article ي Zh | WPRIM | ID: wpr-637964
المكتبة المسؤولة: WPRO
ABSTRACT
Background Choroidal neovascularization (CNV) is a common pathological basis of many ocular fundus diseases.Some treating methods are proved to be effective on CNV but there exist their own shortages.Celecoxib can inhibit experimental neovescularization.Sustained release drug of celecoxib and application approach can offer a basis for the therapy of CNV.Objective This study was to evaluate the sustained release ability of celecoxib-poly lactide-co-glycolide microsphere (CEL-PLGA-MS) in vitro and its inhibitory ability on experimental CNV in vivo.Methods CEL-PLGA-MS was prepared by Hebei Medical University and examined under the scanning electron microscope.The size of CEL-PLGA-MS was measured by Laser Particle Size Analyzer.The drugloading in vitro releasing was monitored by high performance liquid chromatograph (HPLC).Experimental CNV was induced by laser photocoagulation of retina in the right eyes of 72 male brown Norway (BN) rats and then were randomized into the CEL-PLGA-MS group,celecoxib group,blank PLGA group and PBS group.CEL-PLGA-MS with 320 μmol/L celecoxib,80 μmol/L celecoxib,blank PLGA microspheres solution and 0.01 mol/L PBS was intravitreally injected separately according to the grouping.CNV was assessed by fundus fluorescein angiography (FFA) on the 14th day after injection.The fibrovascular proliferation (FVP) thickness at photocoagulation spots was measured by OCT.The retinal pigment epithelium (RPE)-choroid-sclera sections were prepared for the histopathologieal examination of FVP.On the 7th and 28th day after intravitreal injection,the relative expression levels of VEGF mRNA and COX-2 mRNA in the photocoagulation area were detected by reverse transcription PCR (RTPCR).The use and feeding of the experimental animals were followed by the ARVO statement.Results CELPLGA-MS showed the spherical shape with the mean size of 2 467.9 nm and the drug-loading of 7.77% and the drugrelease rate of 80.91% in vitro for 45 days.It presented the controllable release characteristics.CEL-PLGA-MS agglomerated in vitreous body after injection.On the 14th day after intravitreal injection,the mean FVP thicknesses were (94.67±4.64),(98.56±4.72),(71.00±4.77),(50.44±3.01) μm in the blank PLGA microspheres group,PBS group,celecoxib group and CEL-PLGA-MS group,respectively,showing significant increases in mean FVP thickness in the blank PLGA microspheres group and PBS group compared with the celecoxib group and CEL-PLGAMS group (all at P<0.01),and the CEL-PLGA-MS group appeared a lower mean FVP thickness value than the celecoxib group (P<0.01).FFA revealed a large number of strong hyperfluorescences at the photocoagulation area in the rat eyes of the blank PLGA microspheres group and PBS group;while only weak hyperfluorescences were seen in the eelecoxib group and CEL-PLGA-MS group.Histopathological examinations verified the same results in the FVP thickness to OCT image.The relative expression levels of COX-2 mRNA and VEGF mRNA in the RPE-choroid-sclera were all significantly elevated in the blank PLGA microspheres group compared with the celecoxib group and CELPLGA-MS group both on the 7th and 28th day after intravitreal injection (all at P<0.01).On the 7th day after injection,the relative expression levels of COX-2 mRNA were lower on the 7th day and the relative expression levels of COX-2 mRNA and VEGF mRNA were higher on the 28th day in the celecoxib group in comparison with the CEL-PLGA-MS group (all at P<0.01).Conclusions CEL-PLGA-MSs are even in size with the spherical shape and controllable release characteristics in vitro.CEL-PLGA-MS can inhibit experimental CNV and was more durable effective than celecoxib after intravitrea] injection.
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النص الكامل: 1 الفهرس: WPRIM نوع الدراسة: Clinical_trials اللغة: Zh مجلة: Chinese Journal of Experimental Ophthalmology السنة: 2016 نوع: Article
النص الكامل: 1 الفهرس: WPRIM نوع الدراسة: Clinical_trials اللغة: Zh مجلة: Chinese Journal of Experimental Ophthalmology السنة: 2016 نوع: Article