Hornof Margit D, Bernkop-Schnürch Andreas
Institute of Pharmaceutical Technology and Biopharmaceutics, Center of Pharmacy, University of Vienna, Althanstr.14, 1090 Vienna, Austria.
J Pharm Sci. 2002 Dec;91(12):2588-92. doi: 10.1002/jps.10258.
It was the aim of this study to investigate the permeation enhancing effect of thiolated polycarbophil on the cornea of rabbits in vitro. The proposed reaction mechanism involves the opening of the tight junctions in the corneal epithelium. The modification of polycarbophil was achieved via covalent attachment of L-cysteine mediated by a carbodiimide. Transcorneal permeation studies were performed in Ussing-type diffusion chambers. As model compounds, sodium fluorescein, as a marker for paracellular transport, and dexamethasone phosphate were used. To evaluate potential corneal damage the corneal hydration level of each cornea was determined. Polycarbophil-cysteine was found to increase the permeation of sodium fluorescein 2.2-fold and that of dexamethasone phosphate 2.4-fold in comparison to the unmodified polymer. The concentration of dexamethasone in the acceptor medium was 1.5-fold increased. As evidenced by the corneal hydration level, polycarbophil-cysteine did not damage the corneal tissues. Therefore, polycarbophil-cysteine conjugates seem to be promising excipients for ocular drug delivery systems where they might be used as safe permeation enhancers.
本研究旨在体外研究硫醇化聚卡波非对兔角膜的渗透增强作用。提出的反应机制涉及角膜上皮紧密连接的开放。聚卡波非的修饰是通过碳二亚胺介导的L-半胱氨酸共价连接实现的。在Ussing型扩散室中进行经角膜渗透研究。作为模型化合物，使用荧光素钠作为细胞旁转运的标志物，以及地塞米松磷酸酯。为了评估潜在的角膜损伤，测定了每个角膜的角膜水化水平。与未修饰的聚合物相比，发现聚卡波非-半胱氨酸使荧光素钠的渗透率提高了2.2倍，地塞米松磷酸酯的渗透率提高了2.4倍。受体介质中地塞米松的浓度增加了1.5倍。如角膜水化水平所证明的，聚卡波非-半胱氨酸没有损伤角膜组织。因此，聚卡波非-半胱氨酸缀合物似乎是眼用药物递送系统中有前景的辅料，在其中它们可作为安全的渗透增强剂使用。
