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Study of ocular transport of drugs released from a sustained release device.

機譯：從持續(xù)釋放裝置釋放藥物的眼部轉(zhuǎn)運研究。

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Delivering ocular therapeutics to a target site with minimal side effects requires detailed information about the distribution and elimination pathways. This knowledge can guide the development of new drug delivery devices. In this study, we investigated the movement of two drug surrogates, H-110, which is lipophilic, and Gd-DTPA, which is hydrophilic, released from polymer-based implants using a fluorescein technique and magnetic resonance imaging (MRI). We also studied the pharmacokinetics of intravitreally injected triamcinolone acetonide, a low water soluble drug used for treating sight-threatening diseases such as diabetic retinopathy and choroidal neovascularization associated with age-related macular degeneration (AMD).; At 24 hour post implantation, H-110 released from an intravitreal implant was detected in the subretinal space. However, following a subconjunctival implant, very little H-110 fluorescence was detected in the subretinal region. H-110 most likely reached the subretinal space from an intravitreal implant by diffusion through the vitreous and retina. However, most of the H-110 released from a subconjunctival implant is thought to dissipate through the choroidal blood flow.; Concentration profiles of Gd-DTPA, which was released from an intravitreal implant in a New Zealand white rabbit, approached pseudo-steady state within 7 to 8 hours and showed gradients at the rabbit's vitreous-retina border suggesting that diffusion was occurring into the retinal-choroidal-scleral membrane. Parametric analysis with a finite element mathematical model of the rabbit eye yielded for Gd-DTPA a diffusion coefficient of 2.8 x 10-6 cm2/sec in the vitreous and a permeability of 1.0 x 10-5 cm/sec in the composite retina-choroid-sclera membrane. Gd-DTPA concentration decreased away from the implant. Such regional concentration variations throughout the vitreous may have clinical significance when the ubiquitous eye diseases are treated using a single positional implant. Subconjunctival implants in vivo delivered a mean total of 2.7 mug of Gd-DTPA over 8 hours into the vitreous representing only 0.12% of the total amount of compound released from the implant in vitro . No Gd-DTPA was detected in the posterior segment of the eye. Ex vivo, the Gd-DTPA concentration in the vitreous was 30 fold higher suggesting the elimination of significant in vivo barriers to the movement of drugs from the subconjunctival space into the vitreous. (Abstract shortened by UMI.)
機譯：以最小的副作用將眼部治療藥物輸送到目標部位需要有關(guān)分布和消除途徑的詳細信息。這些知識可以指導(dǎo)新的藥物輸送設(shè)備的開發(fā)。在這項研究中，我們研究了兩種藥物替代物的運動，它們是親脂性的H-110和親水的Gd-DTPA，使用熒光素技術(shù)和磁共振成像（MRI）從聚合物基植入物中釋放出來。我們還研究了玻璃體內(nèi)注射曲安奈德丙酮酸的藥代動力學(xué)，曲安奈德是一種水溶性低的藥物，用于治療與年齡相關(guān)性黃斑變性（AMD）相關(guān)的視力障礙疾病，如糖尿病性視網(wǎng)膜病變和脈絡(luò)膜新生血管。植入后24小時，在視網(wǎng)膜下腔中檢測到從玻璃體內(nèi)植入物中釋放的H-110。然而，在結(jié)膜下植入后，在視網(wǎng)膜下區(qū)域幾乎沒有檢測到H-110熒光。 H-110最有可能通過玻璃體和視網(wǎng)膜擴散從玻璃體內(nèi)植入物到達視網(wǎng)膜下腔。然而，大多數(shù)從結(jié)膜下植入物釋放的H-110被認為通過脈絡(luò)膜血流消散。從新西蘭白兔玻璃體內(nèi)植入物中釋放的Gd-DTPA的濃度曲線在7到8小時內(nèi)達到偽穩(wěn)態(tài)，并在兔子的玻璃體-視網(wǎng)膜邊界處顯示梯度，表明擴散正在發(fā)生。脈絡(luò)膜-鞏膜。用兔眼有限元數(shù)學(xué)模型進行參數(shù)分析，得出Gd-DTPA在玻璃體中的擴散系數(shù)為2.8 x 10-6 cm2 / sec，在復(fù)合視網(wǎng)膜脈絡(luò)膜中的滲透率為1.0 x 10-5 cm / sec -鞏膜。 Gd-DTPA濃度遠離植入物而降低。當(dāng)使用單個位置植入物治療普遍存在的眼部疾病時，整個玻璃體中的這種區(qū)域濃度變化可能具有臨床意義。體內(nèi)結(jié)膜下植入物在8小時內(nèi)平均向玻璃體中遞送了總共2.7杯Gd-DTPA，僅占體外植入物釋放的化合物總量的0.12％。在眼后段未檢測到Gd-DTPA。離體，玻璃體內(nèi)的Gd-DTPA濃度高30倍，這表明消除了體內(nèi)顯著的壁壘，阻礙了藥物從結(jié)膜下間隙進入玻璃體的運動。 （摘要由UMI縮短。）

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