Ranta Veli-Pekka, Urtti Arto
Department of Pharmaceutics, University of Kuopio, FIN-70211 Kuopio, Finland.
Adv Drug Deliv Rev. 2006 Nov 15;58(11):1164-81. doi: 10.1016/j.addr.2006.07.025. Epub 2006 Sep 16.
Basic biological research has provided new approaches to treat severe diseases of the retina and choroid, such as age related macular degeneration. Although it is possible to deliver drugs from a subconjunctival drug depot to the retina and choroid, the barriers and kinetics of this route of drug administration are not well known. In this review we investigate the pharmacokinetic aspects of transscleral drug delivery into the posterior eye with emphasis on pharmacokinetic modeling. The existing simulation models related to the transscleral drug delivery are reviewed and future directions for the model development are discussed. In addition, a new simulation model for the transscleral drug delivery based on permeability data is introduced. This compartmental model contains several ocular tissues (sclera, choroid, retinal pigment epithelium and vitreous) and it takes into account the clearance of the drug via choroidal circulation. The model is used to simulate the vitreous delivery of macromolecules based on the available data on FITC-dextran 70 kDa.
基础生物学研究为治疗视网膜和脉络膜的严重疾病,如年龄相关性黄斑变性,提供了新方法。尽管可以从结膜下药物储存库将药物递送至视网膜和脉络膜,但这种给药途径的屏障和动力学尚不清楚。在本综述中,我们研究经巩膜药物递送进入眼后部的药代动力学方面,重点是药代动力学建模。回顾了与经巩膜药物递送相关的现有模拟模型,并讨论了模型开发的未来方向。此外,还介绍了一种基于通透性数据的经巩膜药物递送新模拟模型。该房室模型包含几个眼组织(巩膜、脉络膜、视网膜色素上皮和玻璃体),并考虑了药物通过脉络膜循环的清除。该模型用于根据关于70 kDa异硫氰酸荧光素葡聚糖的现有数据模拟大分子的玻璃体递送。