帕唑帕尼，一种多靶点酪氨酸激酶抑制剂，可减少糖尿病性视网膜血管白细胞淤滞和渗漏。
Pazopanib, a multitargeted tyrosine kinase inhibitor, reduces diabetic retinal vascular leukostasis and leakage.
机构信息
Nanomedicine and Drug Delivery Laboratory, Department of Pharmaceutical Sciences, Aurora, CO 80045, USA.
出版信息
Microvasc Res. 2011 Nov;82(3):346-50. doi: 10.1016/j.mvr.2011.09.001. Epub 2011 Sep 16.
Abstract
OBJECTIVE
To determine the efficacy of pazopanib eye drops in the streptozotocin induced diabetic retinopathy rat model.
METHODS
A 0.5% w/v pazopanib suspension was prepared in phosphate buffered saline (PBS, pH 7.4) in the presence of 0.5% w/v sodium carboxymethyl cellulose. Brown Norway rats were divided into three groups (n=4) - (1) healthy, (2) diabetic, and (3) diabetic with treatment. The drug suspension was administered twice daily as eye drops to group 3 for 30 days. Efficacy parameters including the number of adherent leukocytes in the retinal vasculature (leukostasis), blood-retinal FITC-dextran leakage, and vitreous-to-plasma protein ratio were measured.
RESULTS
Pazopanib suspension in the form of eye drops significantly reduced leukostasis (32%), FITC-dextran leakage (39%), and the vitreous-to-plasma protein ratio (64%) in diabetic animals compared to untreated diabetic group.
CONCLUSION
Pazopanib eye drops can alleviate retinal complications of diabetic retinopathy.
摘要
目的
评估帕唑帕尼滴眼液在链脲佐菌素诱导的糖尿病性视网膜病变大鼠模型中的疗效。
方法
在磷酸盐缓冲盐水（PBS，pH7.4）中制备 0.5% w/v 的帕唑帕尼混悬液，同时存在 0.5% w/v 的羧甲基纤维素钠。将褐家鼠分为三组（n=4）-（1）健康组，（2）糖尿病组，和（3）糖尿病治疗组。药物混悬液以滴眼液的形式每日两次施用于第 3 组 30 天。评估疗效参数包括视网膜血管中的黏附白细胞数（白细胞淤滞）、血视网膜 FITC-葡聚糖渗漏和玻璃体液-血浆蛋白比。
结果
与未治疗的糖尿病组相比，帕唑帕尼滴眼液混悬液形式显著降低了糖尿病动物的白细胞淤滞（32%）、FITC-葡聚糖渗漏（39%）和玻璃体液-血浆蛋白比（64%）。
结论
帕唑帕尼滴眼液可减轻糖尿病性视网膜病变的视网膜并发症。
相似文献
1
Pazopanib, a multitargeted tyrosine kinase inhibitor, reduces diabetic retinal vascular leukostasis and leakage.帕唑帕尼，一种多靶点酪氨酸激酶抑制剂，可减少糖尿病性视网膜血管白细胞淤滞和渗漏。
Microvasc Res. 2011 Nov;82(3):346-50. doi: 10.1016/j.mvr.2011.09.001. Epub 2011 Sep 16.
2
Delivery of SAR 1118 to the retina via ophthalmic drops and its effectiveness in a rat streptozotocin (STZ) model of diabetic retinopathy (DR).通过眼药水将SAR 1118递送至视网膜及其在糖尿病视网膜病变（DR）大鼠链脲佐菌素（STZ）模型中的有效性。
Invest Ophthalmol Vis Sci. 2010 Oct;51(10):5198-204. doi: 10.1167/iovs.09-5144. Epub 2010 May 5.
3
Effects of peroxisome proliferator-activated receptor gamma and its ligand on blood-retinal barrier in a streptozotocin-induced diabetic model.过氧化物酶体增殖物激活受体γ及其配体对链脲佐菌素诱导的糖尿病模型血视网膜屏障的影响
Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4547-52. doi: 10.1167/iovs.05-1432.
4
VEGF164 is proinflammatory in the diabetic retina.血管内皮生长因子164（VEGF164）在糖尿病视网膜中具有促炎作用。
Invest Ophthalmol Vis Sci. 2003 May;44(5):2155-62. doi: 10.1167/iovs.02-0807.
5
Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina.玻璃体内注射皮质类固醇可减轻实验性糖尿病视网膜病变中的白细胞淤滞和血管渗漏。
Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1440-4. doi: 10.1167/iovs.04-0905.
6
Effect of diabetes on transscleral delivery of celecoxib.糖尿病对塞来昔布经巩膜给药的影响。
Pharm Res. 2009 Feb;26(2):404-14. doi: 10.1007/s11095-008-9757-2. Epub 2008 Nov 6.
7
Single periocular injection of celecoxib-PLGA microparticles inhibits diabetes-induced elevations in retinal PGE2, VEGF, and vascular leakage.单次眼周注射塞来昔布 - 聚乳酸 - 羟基乙酸共聚物（PLGA）微粒可抑制糖尿病引起的视网膜前列腺素E2（PGE2）、血管内皮生长因子（VEGF）升高以及血管渗漏。
Invest Ophthalmol Vis Sci. 2006 Mar;47(3):1149-60. doi: 10.1167/iovs.05-0531.
8
Inducible nitric oxide synthase isoform is a key mediator of leukostasis and blood-retinal barrier breakdown in diabetic retinopathy.诱导型一氧化氮合酶亚型是糖尿病视网膜病变中白细胞淤滞和血视网膜屏障破坏的关键介质。
Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5257-65. doi: 10.1167/iovs.07-0112.
9
Effective and selective prevention of retinal leukostasis in streptozotocin-induced diabetic rats using gliclazide.使用格列齐特有效且选择性地预防链脲佐菌素诱导的糖尿病大鼠视网膜白细胞停滞。
Diabetologia. 2002 May;45(5):735-9. doi: 10.1007/s00125-002-0820-y. Epub 2002 Apr 5.
10
Topical pazopanib blocks VEGF-induced vascular leakage and neovascularization in the mouse retina but is ineffective in the rabbit.局部应用帕唑帕尼可阻断小鼠视网膜中 VEGF 诱导的血管渗漏和新生血管形成，但对兔无效。
Invest Ophthalmol Vis Sci. 2013 Jan 21;54(1):503-11. doi: 10.1167/iovs.12-10473.
引用本文的文献
1
Tyrosine Kinase Inhibitors and their role in treating neovascular age-related macular degeneration and diabetic macular oedema.酪氨酸激酶抑制剂及其在治疗新生血管性年龄相关性黄斑变性和糖尿病性黄斑水肿中的作用。
Eye (Lond). 2023 Dec;37(18):3725-3733. doi: 10.1038/s41433-023-02610-z. Epub 2023 Jun 7.
2
BIBF1120 Protects against Diabetic Retinopathy through Neovascularization-Related Molecules and the MAPK Signaling Pathway.BIBF1120通过与新生血管形成相关的分子和丝裂原活化蛋白激酶信号通路预防糖尿病视网膜病变。
J Ophthalmol. 2023 Apr 28;2023:7355039. doi: 10.1155/2023/7355039. eCollection 2023.
3
forming oxygen/ROS-responsive niche-like hydrogel enabling gelation-triggered chemotherapy and inhibition of metastasis.形成对氧/活性氧应答的类微环境水凝胶，实现凝胶化触发的化疗并抑制转移。
Bioact Mater. 2022 Aug 16;21:86-96. doi: 10.1016/j.bioactmat.2022.08.002. eCollection 2023 Mar.
4
Implantable anti-angiogenic scaffolds for treatment of neovascular ocular pathologies.用于治疗新生血管性眼病的可植入抗血管生成支架。
Drug Deliv Transl Res. 2020 Oct;10(5):1191-1202. doi: 10.1007/s13346-020-00753-0.
5
Anti-angiogenic Therapy for Retinal Disease.视网膜疾病的抗血管生成疗法
Handb Exp Pharmacol. 2017;242:271-307. doi: 10.1007/164_2016_78.
6
Novel pharmacotherapies in diabetic retinopathy.糖尿病视网膜病变的新型药物疗法。
Middle East Afr J Ophthalmol. 2015 Apr-Jun;22(2):164-73. doi: 10.4103/0974-9233.154389.
7
Animal models of diabetic retinopathy: summary and comparison.糖尿病性视网膜病变的动物模型：综述与比较。
J Diabetes Res. 2013;2013:106594. doi: 10.1155/2013/106594. Epub 2013 Oct 27.
8
Self-assembled phenylalanine-α,β-dehydrophenylalanine nanotubes for sustained intravitreal delivery of a multi-targeted tyrosine kinase inhibitor.自组装苯丙氨酸-α，β-脱水苯丙氨酸纳米管用于持续眼内递送多靶点酪氨酸激酶抑制剂。
J Control Release. 2013 Dec 28;172(3):1151-60. doi: 10.1016/j.jconrel.2013.09.016. Epub 2013 Sep 25.
9
Safety and efficacy of the multitargeted receptor kinase inhibitor pazopanib in the treatment of corneal neovascularization.多靶点受体激酶抑制剂帕唑帕尼治疗角膜新生血管的安全性和有效性。
Invest Ophthalmol Vis Sci. 2013 Jan 17;54(1):537-44. doi: 10.1167/iovs.12-11032.
10
Topical pazopanib blocks VEGF-induced vascular leakage and neovascularization in the mouse retina but is ineffective in the rabbit.局部应用帕唑帕尼可阻断小鼠视网膜中 VEGF 诱导的血管渗漏和新生血管形成，但对兔无效。
Invest Ophthalmol Vis Sci. 2013 Jan 21;54(1):503-11. doi: 10.1167/iovs.12-10473.
本文引用的文献
1
Anti-angiogenic effects of the receptor tyrosine kinase inhibitor, pazopanib, on choroidal neovascularization in rats.帕唑帕尼（一种受体酪氨酸激酶抑制剂）对大鼠脉络膜新生血管的抗血管生成作用。
Eur J Pharmacol. 2011 Sep;666(1-3):12-8. doi: 10.1016/j.ejphar.2011.05.016. Epub 2011 May 20.
2
Delivery of SAR 1118 to the retina via ophthalmic drops and its effectiveness in a rat streptozotocin (STZ) model of diabetic retinopathy (DR).通过眼药水将SAR 1118递送至视网膜及其在糖尿病视网膜病变（DR）大鼠链脲佐菌素（STZ）模型中的有效性。
Invest Ophthalmol Vis Sci. 2010 Oct;51(10):5198-204. doi: 10.1167/iovs.09-5144. Epub 2010 May 5.
3
Delivery of celecoxib for treating diseases of the eye: influence of pigment and diabetes.塞来昔布眼部疾病治疗的递药系统：色素和糖尿病的影响。
Expert Opin Drug Deliv. 2010 May;7(5):631-45. doi: 10.1517/17425241003663236.
4
Suppression and regression of choroidal neovascularization by the multitargeted kinase inhibitor pazopanib.多靶点激酶抑制剂帕唑帕尼对脉络膜新生血管的抑制与消退作用
Arch Ophthalmol. 2009 Apr;127(4):494-9. doi: 10.1001/archophthalmol.2009.27.
5
Effect of diabetes on transscleral delivery of celecoxib.糖尿病对塞来昔布经巩膜给药的影响。
Pharm Res. 2009 Feb;26(2):404-14. doi: 10.1007/s11095-008-9757-2. Epub 2008 Nov 6.
6
Vascular endothelial growth factor in eye disease.眼部疾病中的血管内皮生长因子
Prog Retin Eye Res. 2008 Jul;27(4):331-71. doi: 10.1016/j.preteyeres.2008.05.001. Epub 2008 May 28.
7
Pharmacotherapies for diabetic retinopathy: present and future.糖尿病视网膜病变的药物治疗：现状与未来
Exp Diabetes Res. 2007;2007:52487. doi: 10.1155/2007/52487.
8
Strategies for blocking angiogenesis in diabetic retinopathy: from basic science to clinical practice.糖尿病视网膜病变中抗血管生成的策略：从基础科学到临床实践
Expert Opin Investig Drugs. 2007 Aug;16(8):1209-26. doi: 10.1517/13543784.16.8.1209.
9
Single periocular injection of celecoxib-PLGA microparticles inhibits diabetes-induced elevations in retinal PGE2, VEGF, and vascular leakage.单次眼周注射塞来昔布 - 聚乳酸 - 羟基乙酸共聚物（PLGA）微粒可抑制糖尿病引起的视网膜前列腺素E2（PGE2）、血管内皮生长因子（VEGF）升高以及血管渗漏。
Invest Ophthalmol Vis Sci. 2006 Mar;47(3):1149-60. doi: 10.1167/iovs.05-0531.
10
Retinal delivery of celecoxib is several-fold higher following subconjunctival administration compared to systemic administration.与全身给药相比，结膜下给药后塞来昔布的视网膜递送量高出数倍。
Pharm Res. 2004 Oct;21(10):1797-804. doi: 10.1023/b:pham.0000045231.51924.e8.
Zotero 插件