Friedrich S, Cheng Y L, Saville B
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Ontario, Canada.
Ann Biomed Eng. 1997 Mar-Apr;25(2):303-14. doi: 10.1007/BF02648045.
Direct intravitreal injection of drug is a common method for treating diseases of the retina or vitreous. The stagnant nature of the vitreous humor and surrounding tissue barriers creates concentration gradients within the vitreous that must be accounted for when developing drug therapy. The objective of this research was to study drug distribution in the vitreous humor of the rabbit eye after an intravitreal injection, using a finite element model. Fluorescein and fluorescein glucuronide were selected as model compounds due to available experimental data. All required model parameters were known except for the permeability of these compounds through the retina, which was determined by fitting model predictions to experimental data. The location of the intravitreal injection in the experimental studies was not precisely known; therefore, several injection locations were considered, and best-fit retinal permeability was determined for each case. Retinal permeability of fluorescein and fluorescein glucuronide estimated by the model ranged from 1.94 x 10(-5) to 3.5 x 10(-5) cm s(-1) and from 0 to 7.62 x 10(-7) cm s(-1), respectively, depending on the assumed site of the injection. These permeability values were compared with values previously calculated from other models, and the limitations of the models are discussed. Intravitreal injection position was found to be an important variable that must be controlled in both experimental and clinical settings.
直接玻璃体内注射药物是治疗视网膜或玻璃体疾病的常用方法。玻璃体液的停滞性质和周围组织屏障在玻璃体内形成了浓度梯度，在开发药物治疗方法时必须加以考虑。本研究的目的是使用有限元模型研究兔眼玻璃体内注射后药物在玻璃体液中的分布情况。由于有可用的实验数据，选择荧光素和荧光素葡糖醛酸作为模型化合物。除了这些化合物通过视网膜的渗透率外，所有所需的模型参数都是已知的，该渗透率通过将模型预测与实验数据拟合来确定。实验研究中玻璃体内注射的位置并不确切知道；因此，考虑了几个注射位置，并针对每种情况确定了最佳拟合视网膜渗透率。根据假设的注射部位，模型估计的荧光素和荧光素葡糖醛酸的视网膜渗透率分别为1.94×10^(-5)至3.5×10^(-5) cm s^(-1)和0至7.62×10^(-7) cm s^(-1)。将这些渗透率值与先前从其他模型计算的值进行了比较，并讨论了模型的局限性。发现玻璃体内注射位置是一个重要变量，在实验和临床环境中都必须加以控制。
