Study of ocular transport of drugs released from an intravitreal implant using magnetic resonance imaging
Study of ocular transport of drugs released from an intravitreal implant using magnetic resonance imaging
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DOI：
10.1007/s10439-005-8974-7
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发表时间：
2005-02-01
影响因子：
3.8
通讯作者：
Lutz, RJ
中科院分区：
文献类型：
--
作者：
Kim, H;Lizak, MJ;Lutz, RJ
确保治疗剂在眼中的最佳递送需要关于可用的转运机制和消除途径的详细信息。这些知识可以指导新药物输送装置的开发。在这项研究中，我们使用T-1加权磁共振成像（MRI）研究了从基于聚合物的植入物中释放的药物替代物Gd-DTPA（Magnevist（（R）在兔玻璃体中的运动。通过与校准样本进行比较，将MRI数据中的强度值转换为浓度。接近伪稳态的浓度曲线显示从植入物向视网膜表面的梯度，表明扩散发生在视网膜-脉络膜-巩膜（RCS）膜中。Gd-DTPA浓度从植入物附近的高值变化到植入物远端的低值。当试图使用单个定位植入物治疗普遍存在的眼部疾病时，整个玻璃体的这种区域浓度差异可能具有临床意义。我们建立了兔眼的有限元数学模型，并将MRI实验浓度数据与模拟浓度曲线进行了比较。该模型利用玻璃体中Gd-DTPA的扩散系数为2.8 x 10（-6）cm（2）s（-1），并产生Gd-DTPA通过模拟复合后膜（代表视网膜-脉络膜巩膜膜）的扩散系数为6.0 x 10（-8）cm（2）s（-1）。由于模型膜的厚度为0.03 cm，因此有效膜渗透率为2.0 x 10（-6）cm s（-1）。Gd-DTPA的对流运动被证明对浓度分布的影响最小，因为该系统的Peclet数为0.09。
Ensuring optimum delivery of therapeutic agents in the eye requires detailed information about the transport mechanisms and elimination pathways available. This knowledge can guide the development of new drug delivery devices. In this study, we investigated the movement of a drug surrogate, Gd-DTPA( Magnevist((R))) released from a polymer-based implant in rabbit vitreous using T-1-weighted magnetic resonance imaging (MRI). Intensity values in the MRI data were converted to concentration by comparison with calibration samples. Concentration profiles approaching pseudosteady state showed gradients from the implant toward the retinal surface, suggesting that diffusion was occurring into the retinal-choroidal-scleral (RCS) membrane. Gd-DTPA concentration varied from high values near the implant to lower values distal to the implant. Such regional concentration differences throughout the vitreous may have clinical significance when attempting to treat ubiquitous eye diseases using a single positional implant. We developed a finite element mathematical model of the rabbit eye and compared the MRI experimental concentration data with simulation concentration profiles. The model utilized a diffusion coefficient of Gd-DTPA in the vitreous of 2.8 x 10(-6) cm(2) s(-1) and yielded a diffusion coefficient for Gd-DTPA through the simulated composite posterior membrane ( representing the retina-choroid sclera membrane) of 6.0 x 10(-8) cm(2) s(-1). Since the model membrane was 0.03-cm thick, this resulted in an effective membrane permeability of 2.0 x 10(-6) cm s(-1). Convective movement of Gd-DTPA was shown to have minimal effect on the concentration profiles since the Peclet number was 0.09 for this system.