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1.
玻璃体内注射包载盐酸去甲万古霉素的聚N-异丙基丙烯酰胺-聚氧化乙烯纳米粒治疗兔眼混合细菌性眼内炎的效果 总被引:1,自引:1,他引:0
目的 探讨玻璃体腔内注射包栽盐酸去甲万古霉素(norvancomycin,NV)的聚N-异丙基丙烯酰胺-聚氧化乙烯[poly(N-isopropyl acrylamide)-polyethylene oxide,PNIPAAm-PEO]纳米缓释给药系统(NV-PNIPAAm-PEO)治疗兔混合细菌性眼内炎模型的效果.方法 选取健康成年新西兰兔50只,每只随机选取1眼向玻璃体腔内注入100×103CFU·L-1的金黄色葡萄球菌和大肠埃希杆菌混合悬液建立眼内炎模型.建模成功后24 h,将实验动物随机分为1个空白对照组(A组)和4个实验组(B组、C组、D组和E组),每组10眼.A组不作任何处理;B组、C组、D组和E组分别向玻璃体腔内注入0.1 mL的空白纳米粒(20 g·L-1)、无菌生理盐水、盐酸去甲万古霉素原药(4.4 g·L-1)和NV-PNIPAAm-PEO(20 g·L-1).于给药后第1、2、3、7、14、21、28、42天分别进行临床炎症评分、眼部A/B超检查及组织病理学检查.结果 A组、B组和C组各时间点眼内炎病变程度无明显差异;D组和E组炎性反应较A组、B组和C组轻(P<0.005);E组与D组在术后21 d内无差异,21 d后E组玻璃体腔混浊程度较D组明显减轻(P<0.005).眼部A/B超检查,术后7 d之后A组、B组和C组可见玻璃体内团块状回声伴点状或短线状回声点;D组在42 d后仍可见玻璃体腔轻度混浊;E组注药后7-14 d可见玻璃体内点线状回声,回声强度较同时期A组、B组和C组弱,21 d后未见明显异常回声.组织病理学检查见A组、B组和C组眼球结构被破坏,D组近后极部视盘前方玻璃体腔内少量淋巴细胞及浆细胞浸润,E组眼球结构正常,未见典型炎性细胞.结论 NV-PNIPAAm-PEO纳米粒玻璃体腔注射治疗细茵性眼内炎疗效确切,与单纯盐酸去甲万古霉素眼内注射相比,具有缓释及药效持久等特性. 相似文献
2.
背景 传统给药方法治疗眼内炎症时,药物难以透过血-视网膜屏障而达到有效的治疗浓度,局部药物缓释系统可以减少用药剂量并降低药物的毒性作用,构建载药药物缓释系统对眼内感染性疾病的治疗具有重要意义. 目的 评价多聚体材料聚N-异丙基丙烯酰胺-聚氧化乙烯(PNIPAAm-PEO)构建的盐酸去甲万古霉素-PNIPAAm-PEO(NV-PNIPAAm-PEO)纳米粒在兔眼玻璃体腔内注射给药后的眼部毒理学和眼内药代动力学特征,为眼后节给药治疗感染性眼病提供依据. 方法 NV-PNIPAArn-PEO纳米粒平均载药量约为质量分数22%,用无菌生理盐水配成质量浓度为20 g/L的凝胶液.新西兰白兔41只采用随机数字表法分为实验组31只和对照组10只,将20 g/L NV-PNIPAAm-PEO凝胶液0.1 ml注射入实验组兔的一侧眼玻璃体腔内,对照组注入等容量的生理盐水.分别于给药后的第1、2、3、7、14、21和28天进行眼前后节裂隙灯显微镜和B型超声检查,记录实验眼的视网膜电图(ERG)反应,对角膜、虹膜、玻璃体和视网膜组织行组织病理学检查,以评价NV-PNIPAAm-PEO对眼部组织结构和功能的影响.将兔眼角膜和视网膜脉络膜制备组织匀浆,收集兔房水、玻璃体和血浆样本,用高效液相色谱分析(HPLC)法检测上述各组织中的药物质量浓度.结果 NV-PNIPAAm-PEO玻璃体腔内注射后1~28 d,裂隙灯显微镜下可见眼前后节组织正常,B型超声检查未见异常;最大混合ERG b波振幅、a波振幅和峰潜时在两组间的差异均无统计学意义(P>0.05).视网膜组织病理学检查表明,两组兔玻璃体腔内注射后视网膜结构均正常.HPLC法分析表明,注射后1~28d,兔眼角膜组织中药物质量分数均低于检测水平下限,血浆药物质量浓度最高为(0.34±0.11) mg/L,房水药物质量浓度为(0.08±0.04)~(2.16±0.07) mg/L,视网膜脉络膜中药物质量分数为(0.11±0.02)~(2.54±0.38)μg/g,玻璃体药物质量浓度为(5.65±1.14) ~ (406.69±21.05) mg/L,21d内玻璃体腔内药物质量浓度高于大多数革兰阳性菌的最低抑菌质量浓度. 结论 载药量约为22% NV-PNIPAAm-PEO纳米粒在兔眼玻璃体腔内注射未见明显眼内毒性反应,玻璃体腔内可维持有效药物质量浓度时间达21d,NV-PNIPAAm-PEO纳米粒是治疗眼内感染较好的缓释给药方法. 相似文献
3.
地塞米松-PLGA纳米粒兔眼玻璃体内注射的药物代谢动力学 总被引:1,自引:0,他引:1
目的地塞米松(dexamethasone,DM)是眼科临床常用药物,但目前缺乏高效、低毒的给药途径。借助生物降解性多聚体材料聚乳酸-羟乙酸(PLGA)构建DM-PLGA纳米粒,兔眼玻璃体内注射可望在眼后节较长时间维持稳定的有效药物浓度。方法乳化/溶剂蒸发法制备载药量分别为20%和50%的DM-PLGA纳米粒,兔眼玻璃体内注射给药后于第1、7、14和21d分别进行临床观察和组织药物浓度的高效液相色谱分析。结果给药后21d内,角膜和房水中药物浓度均低于检测水平下限(10μg·L-1);血浆药物浓度最高为024mg·L-1;载药量20%和50%的2组中视网膜脉络膜药物浓度分别为011-0.42mg·L-1和0.38-0.88mg·L-1,玻璃体药物浓度分别为0.82-26.52mg·L-1和1.78-85.72mg·L-1。临床观察眼底未见异常。结论载药量50%组的DM-PLGA纳米粒在兔眼玻璃体内可维持药物浓度达3周,提示具有眼内注射应用的潜力。 相似文献
4.
地塞米松-聚乳酸-羟基乙酸纳米粒玻璃体内注射对激光诱导的大鼠脉络膜新生血管的抑制作用 总被引:1,自引:0,他引:1
目的观察生物降解性多聚体材料聚乳酸-羟基乙酸(PLGA)包载的醋酸地塞米松(DA)(DA-PLGA)纳米粒玻璃体内注射对实验性脉络膜新生血管(CNV)的抑制效果,评价药物在玻璃体内的释药模式及其对视网膜的毒性反应。方法采用改良的乳化/溶剂蒸发法制备载药量为50%的DA-PLGA纳米粒。雄性BN大鼠54只,每只动物随机选取一只眼作为实验眼,采用激光光凝法建立CNV模型。随机分为DA-PLGA纳米粒组(24只)、DA组(24只)及生理盐水对照组(6只),分别给予实验眼玻璃体内注射DA-PLGA纳米粒10μl(含DA 100μg)、DA 10μl(含DA 100μg)及10μl生理盐水。于激光光凝后1、3、14、21、28、56 d,采用反相高效液相色谱法(RP-HPLC)检测大鼠实验眼玻璃体内DA药物浓度。激光光凝后14、56 d,通过荧光素眼底血管造影(FFA)观察CNV的生成率;之后处死动物,摘除眼球制作标本,进行光学显微镜和电子显微镜观察。结果DA-PLGA纳米粒在眼内释药模式呈4相,即初始突释、稳态释药、第三相突释和渐弱释药,持续释药时间近2个月。激光光凝后14 d,DA-PLGA纳米粒组、DA组和对照组CNV生成率分别为28.2%、31.6%和66.7%。经χ2检验,DA-PLGA纳米粒组和DA组CNV生成率较对照组明显降低(P<0.01)。激光光凝后56 d,光凝区纤维血管组织增生(FVP)的平均厚度在DA-PLGA纳米粒组、DA组和对照组中分别为(69.52±10.52)、(70.49±12.39)、(105.11±13.70)μm。经SNK-q检验,DA-PLGA纳米粒组和DA组FVP的厚度较对照组显著变薄(P<0.01)。激光光凝后14 d,透射电子显微镜检查发现,DA组节细胞层和神经纤维层的线粒体明显空泡化,内质网肿胀,高尔基复合体排列紊乱,微管及微丝排列紊乱。结论玻璃体内注射DA-PLGA纳米粒可以明显抑制实验性CNV的生长。与DA相比,DA-PLGA纳米粒具有药物毒性低、缓释及药效长久等特性。 相似文献
5.
Roberta P. A. Manzano Gholam A. Peyman Petros E. Carvounis Muhamet Kivilcim Palwasha Khan Patricia Chevez-Barrios Walter Takahashi 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2008,246(6):907-911
Purpose To evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira) in the rabbit eye.
Methods Twelve New Zealand albino rabbits received unilateral intravitreous injections of 0.1 ml of adalimumab 0.25 mg (three eyes),
0.50 mg (three eyes), 1.0 mg (three eyes) or 0.1 ml balanced salt solution (BSS, threeeyes). Slit-lamp biomicroscopy and fundoscopy
were carried out at baseline, day 1, 7 and 14 following intravitreous injection, while electroretinography (ERG) was carried
out at baseline and day 14. Animals were euthanized on day 14, and histopathological examination of the eyes was performed.
Results Slit-lamp biomicroscopy and fundoscopy were normal in eyes having received BSS, 0.25 mg or 0.50 mg adalimumab; however, inflammation
was present in two of three eyes having received 1.0 mg adalimumab. Similarly, comparison of scotopic and photopic ERG light
at baseline and day 14 demonstrated no changes in eyes receiving BSS, 0.25 mg or 0.50 mg adalimumab, but two of three eyes
having received 1.0 mg adalimumab showed a greater than 30% reduction in a and b wave. Finally, histopathology demonstrated no differences between eyes receiving BSS, 0.25 mg or 0.50 mg of adalimumab, but
two of three eyes injected with 1.0 mg demonstrated inflammatory cell infiltration of the vitreous and anterior chamber, with
one of these eyes demonstrating retinal necrosis.
Conclusions Escalating doses of intravitreous adalimumab in rabbit eyes caused no detectable functional or structural ocular toxicity
up to a dose of 0.50 mg. Administration of 1.0 mg in 0.1 ml was associated with an inflammatory reaction and retinal necrosis.
None of the authors has any proprietary interest in any technique or product described herein.
The authors have full control of all primary data and they agree to allow Graefes Archive for Clinical and Experimental Ophthalmology
to review their data. 相似文献
6.
Thompson AM 《Clinical & experimental ophthalmology》2007,35(6):566-577
The ocular toxicity of fluoroquinolones and the risks of their use in the treatment of ocular infection were reviewed. Systematic identification, selection, review and synthesis of published English-language studies relating to fluoroquinolone use and safety in animals and humans was conducted. Although not free of complications, fluoroquinolones are generally safe when used to treat ocular infection. Ocular toxicity appears to be dose-dependent and results from class-effects and specific fluoroquinolone structures. Phototoxicity and neurotoxicity have been reported, and toxic effects on ocular collagen may be associated with Achilles tendinopathy. Corneal precipitation may provide an advantageous drug depot but delay healing and result in corneal perforation in approximately 10% of cases. Although human toxicity studies are limited, the current recommended dose for intracameral injection of ciprofloxacin is less than 25 microg. Intravitreal injections of ciprofloxacin 100 microg, ofloxacin 50 microg/mL, trovafloxacin 25 microg or less, moxifloxacin 160 microg/0.1 mL or less and pefloxacin 200 microg/0.1 mL are considered safe. 相似文献
7.
Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats
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AIM:To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor (VEGF) protein and VEGF mRNA in the retina of diabetic rats.METHODS: Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups, each containing 24 animals and 48 eyes. Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3μL of physiological saline, while in groups B and C were injected with 3μL (75μg) of bevacizumab and 3μL of bevacizumab-chitosan nanoparticles (containing 75μg of bevacizumab), respectively. Immunohistochemistry was used to assess retinal angiogenesis, real-time PCR assay was used to analyse the expression of VEGF mRNA, and light microscopy was used to evaluate the morphology of retinal capillaries.RESULTS:Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A (P>0.05), while theVEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection (P<0.05). Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection (P<0.05) in group B, and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection (P<0.05) in group C. Using multiple comparisons among group A, group B, and group C, the VEGF expression before injection was higher than at 1, 4 and 8 weeks after injection (P<0.05). The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection, and also higher 1 week after injection compared with 4 weeks after injection (P<0.05). No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone.CONCLUSION: The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of bevacizumab inhibits VEGF expression in retina, and bevacizumab-chitosan nanoparticles have a longer duration of action. 相似文献
8.
姜黄素兔眼玻璃体内注射后眼内毒副作用研究 总被引:4,自引:0,他引:4
目的研究不同剂量姜黄素兔眼玻璃体内注射后的眼内毒副作用。方法40只实验兔,随机分为4组,每组10只,一眼为实验眼,玻璃体内分别注射0.05mg/0.1ml、0.1mg,0.1ml、0.2mg,0.1ml姜黄素及0.5‰的DMSO 0.1ml;对侧眼为对照眼,在玻璃体内注射0.1ml生理盐水注射后于第1、第3、第7、第14天进行常规眼部检查和视网膜电图检查:在第3、第7、第14天分别摘取2只眼球做光学和透射电子显微镜检查。结果0.2mg组在注药后第3天和第7天,实验眼暗适应视网膜电图a波振幅分别为(129±9)μV和(131±11)μV,与对照眼的(145+13)μV和(146+11)μV相比显著降低(P〈0.01);实验眼b渡振幅分别为(259±9)μV和(257±7)μV,与对照眼的(283±13)μ
V和(276+8)μV相比显著降低(P〈0.01)。第14天时a波和b波振幅又恢复正常,其余各组各时间段,实验眼a波和b波振幅与对照眼相比差异无统计学意义。各时间段常规眼部检查和视网膜组织学栓查正常。结论 姜黄素玻璃体内注射0.2mg以下剂量是安全可行的。 相似文献
9.
Burkhard Wiechens Doris Neumann Joachim B. Grammer Uwe Pleyer Jürgen Hedderich Gernot I.W. Duncker 《International ophthalmology》1998,22(3):133-143
Background: Ofloxacin (OFLX) is a fluoroquinolone-antibiotic with a broad antimicrobial spectrum that may have a potential
role in the treatment of bacterial endophthalmitis. However, its elimination half life after intravitreal injection is short.
To prolong the intravitreal antibacterial level OFLX was incorporated into liposomes. This study was performed to investigate
the retinal toxicity of liposome-incorporated and free OFLX. Materials and methods: OFLX was incorporated into multilamellar
large vesicles. 0,1 ml of this suspension (= 180.2 μg OFLX) was injected into the midvitreous of rabbit eyes (n = 6). Free
OFLX in doses of 100 μg, 500 μg and 1,000 μg was injected into the midvitreous of a second group of rabbit eyes (n = 18).
The other eye served as a control and received empty liposomes or normal saline solution, respectively. Before injection and
at the end of follow-up an ERG was obtained. After a follow-up of 1 day, 14 and 28 days the animals were perfused with glutaraldehyde
and the eyes were examined by light- and transmission electron microscopy. Results: The ERG as well as the histologic studies
did not reveal any pathological changes after injection of liposome-incorporated OFLX compared to the control eyes. Significant
reduction of the ERG was observed after 500 μg free OFLX in 2 out of 6 eyes after 1 and 14 days, respectively, and in 2 eyes
1 day after 1,000 μg free OFLX. Three days after injection of 1,000 μg OFLX the retina showed focal destruction in 1 out of
6 eyes. In another eye with the same dose 14 days after injection the photoreceptor outer segments showed disorganisation.
Conclusion: This study shows that liposome-incorporated OFLX did not have any retinal toxicity in this animal model. Free
OFLX appears to have no retinal toxicity in rabbit eyes at a dose of 100 μg after intravitreal injection. Injection of higher
doses resulted in ERG changes and marked retinal damage.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
10.
目的:研究舒芬太尼对兔眼部用药的急性毒性反应,为其临床局部安全用药提供理论依据。
方法:将16只健康成年新西兰兔随机分成4组。1组为对照组,以空白溶剂作溶媒对照; 2,3,4组家兔左眼分别滴舒芬太尼注射液5μg(2滴,5min内)、7.5μg(3滴,10min内)、10μg(4滴,15min内),同时各组右眼以9g/L NaCl溶液作为自身对照,滴速相同。滴药后的7d后进行局部毒性研究。
结果:肉眼及裂隙灯观察:各组角膜无混浊、结膜无明显充血和水肿、无分泌物、虹膜正常,无产生暂时闭目现象。内皮照相:各组的角膜内皮细胞计数无统计学差异; 光镜观察:结膜、角膜、角巩缘、虹膜、睫状体、视网膜及视神经均未发现有病理形态学损伤。
结论:单次使用5~10μg舒芬太尼眼部给药进行镇静、镇痛在短期内是安全的。 相似文献
11.
足叶乙苷玻璃体内注射对兔视网膜损伤的研究 总被引:1,自引:0,他引:1
目的 研究足叶乙苷(etoposide,Vp-16)兔眼玻璃体内注射对视网膜的化学性损伤作用。方法 28只大白兔,根据足叶乙苷玻璃体内注射的量0μg、1.5μg、15μg、150μg、375μg、750μg、1500μg随机分为7组,每组8眼。注射前1d,注射后1d、3d、7d、12d作视网膜电图(electroretinogram,ERG)检查,12d处死动物,进行病理学光镜及电镜检查。结果 玻璃体内注射足叶乙苷量为0μg、1.5μg、15μg、150μg的4组,在注射前后,其ERG、光镜和电镜检查均未发现明显异常;注射量为375μg、750μg、1500μg的3组,其ERG、光镜和透射电镜检查在注射后均发生了显著的异常改变。结论 足叶乙苷对兔眼视网膜有一定的化学性损伤作用,并且呈剂量依赖性;兔眼玻璃体内注射的安全剂量至少高达150μg。 相似文献
12.
目的评价兔玻璃体腔注射国产美罗培南对敏感菌引起的眼内炎的疗效。方法选取健康成年日本大耳白兔24只,随机分为Ⅰ、Ⅱ两组,每组12只,分别玻璃体腔内接种金黄色葡萄球菌和绿脓杆菌建立相应的眼内炎模型。待出现典型眼内炎体征时,Ⅰ组和Ⅱ组再随机分为A、B组和C、D组。B、D组玻璃体腔均注射美罗培南1.25mg,A、C组分别注射万古霉素1.0mg和复达欣2.0mg作为对照。通过临床炎症评分、细菌培养阳性率、组织学检查病理评分等指标评估药物疗效。结果在两种眼内炎模型中,美罗培南用药后临床炎症评分均有显著下降,用药前后相比有统计学差异,但与万古霉素、复达欣相比无统计学差异;美罗培南用药后细菌培养阳性率在金黄色葡萄球菌和绿脓杆菌眼内炎模型中分别为0和16.7%,均低于万古霉素和复达欣,与万古霉素相比差异有统计学意义;用药2周后组织学检查显示绝大多数标本视网膜组织结构基本完整,层间有不同程度变性和坏死伴炎症细胞浸润,美罗培南与万古霉素、复达欣相比其视网膜病理评分均无统计学差异。结论兔玻璃体腔注射美罗培南治疗敏感金黄色葡萄球菌和绿脓杆菌引起的眼内炎,疗效分别与万古霉素、复达欣基本相当,但当眼内炎体征已明显时单次眼内用药很难完全控制炎症。 相似文献
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目的:评价环孢霉素A(CyA)壳聚糖纳米微粒在兔眼玻璃体腔内的药物代谢动力学。
方法:取实验兔20只分别在植入药后1,2,3,5,7,9,11,14,21,28d,各取2只兔(含4眼),抽取玻璃体用高效液相色谱法检测CyA的药物浓度。
结果:CyA壳聚糖纳米微粒在体外14d内药物累积释放比率为81%。在注入玻璃体腔内28d均可检测到CyA,11d时为最高浓度1237.7ng/mL,最小浓度在第28d测为4485ng/mL。
结论:CyA壳聚糖纳米微粒在玻璃体腔能缓慢释放CyA,有很高的生物利用度。壳聚糖纳米微粒有望成为一种新型的药物载体,用于治疗眼后节疾病。 相似文献