Cannulation of the suprachoroidal space: A novel drug delivery methodology to the posterior segment
Cannulation of the suprachoroidal space: A novel drug delivery methodology to the posterior segment
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DOI：
10.1016/j.ajo.2006.05.045
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发表时间：
2006-11-01
影响因子：
4.2
通讯作者：
Cameron, J. Douglas
中科院分区：
文献类型：
--
作者：
Olsen, Timothy W.;Feng, Xiao;Cameron, J. Douglas
目得：通过在灵长类动物和猪的动物模型中对脉络膜上腔进行微插管，描述、测试和评价一种新型的后部给药系统（PDS）的药代动力学。恒河猴（Macaca mulatta）（n = 1）和猪模型（n = 93）用于评估PDS，PDS是一种将药物递送通道与纤维结合的微插管，光学照明和最佳过渡特性。研究了手术技术、安全性、组织病理学、视网膜和脉络膜血流、示踪染料注射和曲安西龙药代动力学。术前和术后进行高速视频共焦扫描激光检眼镜（cSLO）检查，使用荧光素和吲哚菁绿色（ICG）成像和宽视野眼底成像研究。摘除眼球用于组织病理学或药代动力学研究。结果：94只动物中有93只进行了插管。并发症包括：眼内炎（1/ 94）、脉络膜撕裂（1/94）、脉络膜血流不规则（4/94）、术后炎症（6/94）、巩膜扩张（4/94）、伤口脓肿（1/94）等。组织病理学显示无并发症病例的解剖结构正常。曲安西龙仍然在当地的眼组织至少120天，并在体循环中的非常低的水平可测量的。结论：通过微插管系统，脉络膜上腔可以通过使用仔细的手术技术进行安全和可重复的方式。应避免PDS头端用力撞击黄斑和视神经区域的结缔组织。曲安西龙的药代动力学是独特的，表明长期的局部组织水平与低全身水平。PDS进入脉络膜上腔代表了一种新的药物递送方法，适用于黄斑、视神经和后极的各种药物治疗。
PURPOSE: To describe, test, and evaluate the pharmacokinetics of a novel posterior drug delivery system (PDS) by means of microcannulation of the suprachoroidal space in both the primate and pig animal model.DESIGN: Animal study.METHODS: A rhesus macaque (Macaca mulatta) (n = 1) and pig model (n = 93) were used to evaluate the PDS, a microcannula that combines a drug delivery channel with a fiber, optic illumination and optimal transition properties. The surgical technique, safety profile, histopathology, retinal and choroidal blood flow, injection of tracer dyes, and triamcinolone pharmacokinetics were studied. Prep and postsurgical high-speed video confocal scanning laser ophthalmoscopy (cSLO) that used fluorescein and indocyanine green (ICG) imaging and wide,field fundus imaging studies were performed. Globes were enucleated for either histopathology or pharmacokinetics.RESULTS: Cannulation was performed in 93 of 94 animals. Complications included: endophthalmitis (1/ 94), choroidal tear (1/94), choroidal blood flow irregularities (4/94), postoperative inflammation (6/94), scleral ectasia (4/94), wound abscess (1/94), and others. Histo, pathology demonstrated normal anatomy in uncomplicated cases. Triamcinolone remains in the local ocular tissue for at least 120 days, and measurable at very low levels in the systemic circulation.CONCLUSIONS: Accessing the suprachoroidal space by the microcannulation system can be performed in a safe and reproducible manner by using careful surgical technique. Forceful PDS tip impact into connective tissues in the macular and optic nerve regions should be avoided. Triamcinolone pharmacokinetics are unique and suggest long-term local tissue levels with low systemic levels. PDS access to the suprachoroidal space represents a novel drug delivery method, applicable to a wide variety of pharmacotherapies to the macula, optic nerve, and posterior pole.