来自巩膜外植体的递送。

Delivery from episcleral exoplants.

作者信息

Pontes de Carvalho Ricardo A, Krausse Melissa L, Murphree A Linn, Schmitt Edward E, Campochiaro Peter A, Maumenee Irene H

机构信息

Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-9277, USA.

出版信息

Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4532-9. doi: 10.1167/iovs.06-0030.

DOI:10.1167/iovs.06-0030

PMID:17003449

Abstract

PURPOSE

To assess the impact of an episcleral exoplant on transscleral delivery.

METHODS

New Zealand White rabbits were given a periocular injection of sodium fluorescein (fluorescein, 376 Da) or an episcleral exoplant loaded with fluorescein. Two types of exoplants were tested: (1) a rigid polyethylene device, impermeable on one side and open to the sclera on the other, that contained compressed pellets of fluorescein and was sutured loosely (apposition group) or tightly to indent the sclera (indentation group) and (2) flexible refillable silicone exoplants also open to the sclera that were secured by suturing, to form a sealed episcleral chamber that was filled with a fluorescein solution. Ocular and plasma fluorophotometry were performed at several time points, and histology was performed to evaluate the effect of exoplants on the periocular tissue.

RESULTS

Within 20 minutes of a periocular injection of fluorescein, peak fluorescence was visible in the anterior chamber (AC) and at later time points was displaced toward the retina; at all time points, the highest fluorescence was in the AC. For the polyethylene device indentation group, peak fluorescence was in the retina and posterior vitreous and spread to the AC over time. For the apposition exoplant group, two peaks of fluorescence were seen initially, one in the retina and posterior vitreous and one in the AC. The area under the concentration time curve (AUC +/- SE) for fluorescein concentration was 144.4 +/- 15.1 mug . h/mL for the retinal peak and 43.6 +/- 7.1 mug . h/mL for the posterior vitreous peak after injection of 5 mg of fluorescein into a silicone exoplant, compared with a retinal peak of 3.9 +/- 0.3 and a posterior vitreous peak of 0.99 +/- 0.26 mug . h/mL after periocular injection of 5 mg of fluorescein (P < 0.01 for each). Peak plasma fluorescein levels were significantly reduced in the exoplant group compared with periocular injection.

CONCLUSIONS

An episcleral exoplant facilitates diffusion of fluorescein through the sclera resulting in high levels in the retina and posterior vitreous; levels are markedly increased compared with periocular injection of the same amount of fluorescein. It also reduces peak plasma levels indicating reduction of systemic absorption. This procedure provides a new approach that can be combined with sustained-release preparations to optimize delivery of agents to the retina and choroid while minimizing the potential for systemic toxicity.

摘要

目的

评估巩膜外植入物对经巩膜给药的影响。

方法

给新西兰白兔眼周注射荧光素钠（荧光素，分子量376 Da）或植入负载荧光素的巩膜外植入物。测试了两种类型的植入物：（1）一种刚性聚乙烯装置，一侧不可渗透，另一侧通向巩膜，其中含有压缩的荧光素颗粒，松散缝合（贴附组）或紧密缝合以压迫巩膜（压迫组）；（2）可灵活填充的硅酮植入物，也通向巩膜，通过缝合固定，形成一个充满荧光素溶液的密封巩膜腔。在多个时间点进行眼内和血浆荧光光度测定，并进行组织学检查以评估植入物对眼周组织的影响。

结果

眼周注射荧光素后20分钟内，前房（AC）可见荧光峰值，在随后的时间点荧光向视网膜移动；在所有时间点，AC中的荧光最高。对于聚乙烯装置压迫组，荧光峰值出现在视网膜和玻璃体后部，并随时间扩散到AC。对于贴附植入物组，最初可见两个荧光峰，一个在视网膜和玻璃体后部，一个在AC。将5 mg荧光素注入硅酮植入物后，视网膜峰值荧光素浓度时间曲线下面积（AUC +/- SE）为144.4 +/- 15.1 μg·h/mL，玻璃体后部峰值为43.6 +/- 7.1 μg·h/mL，而眼周注射5 mg荧光素后，视网膜峰值为3.9 +/- 0.3 μg·h/mL，玻璃体后部峰值为0.99 +/- 0.26 μg·h/mL（各P < 0.01）。与眼周注射相比，植入物组的血浆荧光素峰值水平显著降低。