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1.
Intravitreal administration of antisense oligonucleotides: potential of liposomal delivery 总被引:8,自引:0,他引:8
Antisense oligonucleotides are short synthetic fragments of genes that are able to inhibit gene expression after being internalized by cells. They can therefore be used as antiviral compounds particularly, for the treatment of ocular viral infections (i.e. Herpes simplex virus or Cytomegalovirus, CMV). Antisense oligonucleotides are however poorly stable in biological fluids and their intracellular penetration is limited. Although oligonucleotides are now currently used in therapeutics for the treatment of CMV by intravitreal injection (Vitravene) their main drawbacks impose to repeat the number of administrations which can be very harmful and damaging. A system that is able to permit a protection of oligonucleotides against degradation and their slow delivery into the vitreous would be more favorable for improving patient compliance. The use of liposomes for intravitreal administration can be very promising since these lipid vesicles are able to protect oligonucleotides against degradation by nucleases and they allow to increase the retention time of many drugs in the vitreous. In this review, the potentialities of liposomes for the intravitreal delivery of oligonucleotides will be discussed. 相似文献
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Kellner U Kellner S 《Klinische Monatsbl?tter für Augenheilkunde》2011,228(11):1015, 1017-30; quiz 1031-3
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We evaluated the efficacy of microspheres of biodegradable polymers as a slow releasing drug delivery system in the vitreous body. Microspheres containing 5-FU were prepared with polymers of poly-(lactic acid) or copolymers of glycolic acid and lactic acid. The release of the drug was studied in vitro. Poly-(lactic acid) microspheres released 5-FU for 7 days. The intravitreal kinetics of the microspheres was studied in rabbits in vivo. The microspheres disappeared from the vitreous cavity of normal eyes by 48 +/- 5 days after injection. Disappearance was accelerated from the vitreous cavity of vitrectomized rabbits (14 +/- 2 days, p less than 10(-6)). No abnormality was found on electroretinographic or histological examinations after microspheres injection. These results suggested that microspheres of biodegradable polymers could be useful as a potential drug delivery system for sustained drug release in the vitreous body. 相似文献
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碱性成纤维细胞生长因子反义寡核苷酸及其脂质体对体外培养的大鼠晶状体上皮细胞增殖的抑制作用 总被引:1,自引:0,他引:1
目的 探讨碱性成纤维细胞生长因子(bFGF)反义寡核苷酸及其脂质体对大鼠晶状体上皮细胞(LEC)增殖的抑制作用。方法 体外培养大鼠LEC,细胞传代后分别加入bFGF反义和正义寡核苷酸及其脂质体,以营养液和无药脂质体为对照培养24 h后,用噻唑蓝(MTT)法测定细胞的增殖情况,用逆转录聚合酶链反应(RT-PCR)法测定细胞bFGF mRNA的表达情况。结果 大鼠LEC原代培养24 h可见细胞生长,形态为多边形,培养2-3周细胞汇合成片;传代培养细胞可在1~2周汇合成片。MTT法测定显示,bFGF反义寡核苷酸组(Ⅰ组)、正义寡核苷酸组(Ⅱ组)及营养液组(Ⅴ组)的吸光度(A值)分别为0.138±0.074、0.325±0.097及0.370±0.079,Ⅰ组A值显著小于Ⅱ和Ⅴ组(P=0.024,0.005);bFGF反义寡核苷酸脂质体组(Ⅲ组)、正义寡核苷酸脂质体组(Ⅳ组)及无药脂质体组(Ⅵ组)的A值分别为0.128±0.032、0.258±0.120及0.348±0.017,Ⅲ组A值显著小于Ⅵ组(P=0.000)。RT-PCR法检测结果显示,以2μg总RNA为模板,循环30次,bFGF反义寡核苷酸、bFGF正义寡核苷酸及营养液的扩增产物的量分别为0.33、0.99及0.85μg;:bFGF反义寡核苷酸脂质体、bFGF正义寡核苷酸脂质体及无药脂质体的扩增产物的量分别为0.23、0.48及0.56μg。结论大鼠LEC可在体外培养;bFGF反义寡核苷酸及其脂质体可 相似文献
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脂质体易与生物融合,具有很好的生物相容性,且无毒、无免疫原性。对脂质体在眼部给药系统中的应用进行综述,分别从脂质体在眼部局部给药、玻璃体内给药、结膜传递等角度分析了脂质体在眼部给药系统中的最新研究进展。 相似文献
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The use of liposomes as intravitreal drug delivery system 总被引:5,自引:0,他引:5
Liposomes are vesicular lipidic systems allowing encapsulation of drugs. This article reviews the relevant issues in liposome structure (composition and size), and their influence on intravitreal pharmacokinetics. Liposome-mediated drug delivery to the posterior segment of the eye via intravitreal administration has been addressed by several authors and remains experimental. Liposomes have been used for intravitreal delivery of antibiotics, antivirals, antifungal drugs, antimetabolites, and cyclosporin. Encapsulation of these drugs within liposomes markedly increased their intravitreal half-life, and reduced their retinal toxicity. Liposomes have also shown an attractive potential for retinal gene transfer by intravitreal delivery of plasmids or oligonucleotides. 相似文献
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A 49-year-old Mexican male presented with a free-floating cyst in the vitreous. The cyst was removed at the time of cataract surgery and on the first postoperative day a second cyst was found in the anterior chamber. The second cyst was excised by cryoextraction 6 weeks after the initial surgery, but the eye developed an inoperable retinal detachment and phthisis bulbi. Although the diagnosis of cysticercosis was made clinically, initially, the only laboratory evidence for parasitic infection was a peripheral blood eosinophilia. The patient later developed an enlarged liver which was consistent with parasitic infection based on a liver scan. The morphology and life cycle of the parasite is described as well as suggestions for surgical removal. 相似文献
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Intravitreal toxicity of high-dose etanercept. 总被引:2,自引:0,他引:2
Muhamet Kivilcim Gholam A Peyman Abdul Ahad Kazi John Dellacroce Randa N Ghobrial Roberta Monzano 《Journal of ocular pharmacology and therapeutics》2007,23(1):57-62
PURPOSE: The aim of this study was to evaluate the retinal toxicity of high-dose intravitreal etanercept, a U.S. Food and Drug Administration-approved anti-inflammatory drug, in the rabbit model. METHODS: Twenty (20) New Zealand albino rabbits were divided into 5 groups (n=4); eyes in each group were intravitreally injected with one of the following doses of etanercept: 125 microg, 250 microg, 500 microg, 1 mg, or 2.5 mg. One (1) eye in each animal was used for the study dose; the fellow eye was injected with buffered sterile saline as a control. All animals were examined using indirect ophthalmoscopy and slit-lamp biomicroscopy before and after intravitreal injection and at days 1, 7, and 14. Electroretinography (ERG) was performed on all animals before intravitreal injection and 14 days after injection. The animals were euthanized on day 14. Histological preparations of the enucleated eyes were examined with light microscopy for retinal toxicity. RESULTS: Clinical examination, histological evaluation, and ERG results of all 5 groups demonstrated no signs of retinal toxicity. CONCLUSIONS: Intravitreal doses as high as 2.5 mg of etanercept did not cause retinal toxicity. Intravitreal doses of up to 2.5 mg of etanercept may provide a more potent, prolonged effect than the lower doses previously recommended. 相似文献
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Approximately 90% of all ophthalmic drug formulations are now applied as eyedrops. Although eyedrops are convenient and well accepted by patients, about 95% of the drug contained in the drops is lost due to absorption through the conjunctiva or through the tear drainage. A major fraction of the drug eventually enters the bloodstream and may cause side effects. To reduce drug loss and side effects, it is proposed to encapsulate the ophthalmic drug formulations in liposomes and to disperse the drug-laden liposomes in the lens material. Upon insertion into the eye, the liposome-laden lens will slowly release the drug into the pre-lens (the film between the air and the lens) and the post-lens (the film between the cornea and the lens) tear films and thus provide drug delivery for extended periods of time. This paper focuses on dispersing dimyristoyl phosphatidylcholine (DMPC) liposomes in poly-2-hydroxyethyl methacrylate (p-HEMA) hydrogels, which are a common contact lens material. The results of this study show that the p-HEMA gels loaded with liposomes are transparent and that these gels release drugs for a period of about 8 days. Contact lenses made of particle-laden gels are expected to deliver drugs at therapeutic levels for a few days. The delivery rates can be tailored by controlling the particle and the drug loading. 相似文献
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Xiaoguang Dong Weiyun Shi Gongqiang Yuan Lixin Xie Shenguo Wang Ping Lin 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2006,244(4):492-497
Purpose The purpose was to evaluate the efficacy of the intravitreal implantation of the biodegradable cyclosporin A (CsA) drug delivery system (DDS) for experimental chronic uveitis.Methods The DDS was prepared by formulating CsA into glycolide-co-lactide-co-caprolactone copolymer (PGLC). Right eyes of 30 New Zealand white rabbits were used to establish a model of uveitis and randomized into control, intravitreal non-medicated DDS, oral CsA (15 mg/kg daily), and intravitreal CsA-PGLC DDS (each containing 2 mg CsA) groups. The progress of ocular inflammation, results of electroretinography, and histopathological examination of ocular, renal, and hepatic functions were recorded. Intravitreal CsA levels were measured in another 13 rabbits receiving an implant of the CsA-PGLC DDS.Results Chronic uveitis was successfully induced in all 30 eyes. The inflammation in the eyes with no treatment, non-medicated implant, and oral CsA was more severe than those with the CsA-PGLC DDS at each timepoint. The electroretinography b-wave was depressed much less in the CsA-PGLC DDS group than in the other three groups (p<0.05). No renal or hepatic tissue damage was found in eyes with the CsA-PGLC DDS. The mean intravitreal CsA level was 102.2∼145.5 ng/ml at 1∼3 weeks after CsA-PGLC DDS implantation, 491.0∼575.2 ng/ml at 4∼10 weeks, and 257.3 ng/ml at 14 weeks; no toxicity was detected.Conclusion Intravitreal implantation of the biodegradable CsA-PGLC DDS may effectively reduce the intraocular inflammation in rabbits with no toxicity, which provides a potentially safe and convenient approach for the treatment of chronic uveitis. 相似文献
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Intravitreal toxicity of levofloxacin and gatifloxacin. 总被引:1,自引:0,他引:1
Abdul Ahad Kazi Christopher M Jermak Gholam A Peyman Erdinc Aydin Mohammad Riazi-Esfahani 《Ophthalmic surgery, lasers & imaging》2006,37(3):224-229
BACKGROUND AND OBJECTIVE: To assess the retinal toxicity of varying concentrations of intravitreally injected gatifloxacin and levofloxacin. MATERIALS AND METHODS: In this experimental, controlled study, levofloxacin (initial concentration = 25 mg/mL) and gatifloxacin (initial concentration = 2 mg/mL) were titrated using 5% dextrose solution to concentrations of 2,500 to 156 microg/0.1 mL and 400 to 50 microg/0.1 mL, respectively. Each concentration was injected intravitreally into two rabbit eyes (one eye per animal); two control eyes were injected with 0.1 mL of 5% dextrose solution. All animals were examined and electroretinography was performed before and 14 days after injection. The animals were killed at 14 days; the eyes were enucleated and prepared for light microscopy. RESULTS: The levofloxacin group exhibited significant decreases in electroretinography in the eyes injected with 1,250 and 2,500 microg. No signs of retinal toxicity were observed on slit-lamp examination, indirect ophthalmoscopy, or light microscopy in all eyes injected intravitreally with 625 microg or less of levofloxacin or in any eyes given gatifloxacin. CONCLUSION: Intravitreally injected concentrations of 625 microg or less of levofloxacin and 400 microg or less of gatifloxacin appeared nontoxic. 相似文献
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Hyperthermia and temperature-sensitive liposomes: selective delivery of drugs into the eye 总被引:1,自引:0,他引:1
Experiments were performed to quantitate the delivery of two drugs into the eye following hyperthermia. The drugs, cytosine arabinoside and 5-fluorouridine, were encapsulated in temperature-sensitive liposomes. After systemic injection of the liposome-encapsulated drug, microwave hyperthermia was applied to the superior limbus of rabbit eyes in an attempt to locally release the drug. Samples of aqueous humor and vitreous showed significantly higher drug levels in the heated versus the unheated eyes. Histology of the heated eyes showed no significant damage to ocular structures at the power level used to release the entrapped drug. Heating at higher power levels did damage the eye, confirming earlier studies. The potential uses and limitations of this drug delivery modality are discussed. 相似文献
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Intravitreal and subretinal proliferation induced by platelet-rich plasma injection in rabbits. 总被引:4,自引:0,他引:4
R M Pi?on J C Pastor M A Saornil M B Goldaracena A G Layana M J Gayoso J Guisasola 《Current eye research》1992,11(11):1047-1055
We developed an experimental model of proliferative vitreoretinopathy (PVR) in albino rabbits by combining some factors suspected of causing the disease. Sixty nine eyes divided into six groups served as controls (Groups C 1-6). Forty nine eyes were divided into four experimental groups (Groups E 1-4). Group E1 (n = 12) was injected with 0.15 ml of platelet-rich plasma. In addition, Groups E2 (n = 12) and E3 (n = 12) underwent cryotherapy or vitrectomy. Group E4 (n = 13) underwent both procedures. Seven of the 13 Group 4 experimental eyes developed total retinal detachment and giant holes. None of the other groups developed more than two total retinal detachments or giant holes (P < 0.05). Light and electron microscopy showed intravitreal or preretinal proliferation composed of fibroblast-like cells. Retroretinal membranes appeared only in Group E4 eyes, composed of elongated cells with oval nuclei and abundant organelles in the cytoplasm. We believe these lesions mimic human PVR more closely than other models previously developed. 相似文献
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H B Chawla 《The British journal of ophthalmology》1973,57(1):58-59
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Florian Rensch Ulrich H M Spandau Frank Schlichtenbrede Stefan von Baltz Teodosio Libondi Jost B Jonas Urs Vossmerbaeumer 《Ophthalmic surgery, lasers & imaging》2008,39(3):182-185
BACKGROUND AND OBJECTIVE: To evaluate the effect of intravitreal bevacizumab on visual acuity in patients with myopic choroidal neovascularization. PATIENTS AND METHODS: The retrospective case series study included 13 patients with myopic choroidal neovascularization who received three intravitreal injections of 1.5 mg of bevacizumab. RESULTS: At 1, 3, and 6 months after the first injection, mean visual acuity improved significantly from 0.63 +/- 0.41 logarithm of the minimum angle of resolution units (LogMAR) to 0.39 +/- 0.22 (P< .001), 0.47 +/- 0.49 (P= .002), and 0.52 +/- 0.49 LogMAR (P = 0.009), respectively. The increase in visual acuity was correlated with a significant decrease in central retinal thickness (P = .003) as measured by optical coherence tomography. Mean intraocular pressure did not change significantly (P> .05) during follow-up. CONCLUSION: Intravitreal injections of bevacizumab may be a therapeutic option for exudative myopic macular degeneration. 相似文献
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J V Forrester W Edgar C R Prentice C D Forbes J Williamson 《Experimental eye research》1976,22(2):181-188
The fibrinolytic system within experimentally induced vitreous haemorrhages was studied in rabbits. The presence of crosslinked fibrin was noted for up to five weeks following induction of the haemorrhage, while soluble fibrin degradation products were detected in low concentration for two months. Plasminogen activator activity of the vitreous did not decline following vitreous haemorrhage. In addition haemolysis appeared to occur simultaneously with fibrinolysis. It is suggested that fibrinolysis is important in the clearing of blood from the vitreous, and may be the initiating step. 相似文献