Siriwardane Dumindika A, Jiang Wenlei, Mudalige Thilak
Arkansas Laboratory, Office of Regulatory Science, Office of Regulatory Affairs, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
Int J Pharm. 2023 Nov 5;646:123449. doi: 10.1016/j.ijpharm.2023.123449. Epub 2023 Sep 28.
VISUDYNE® is a liposomal formulation of verteporfin, used in the photodynamic therapy of age-related macular degeneration via intravenous administration. In this study, we developed a new in vitro method to quantify verteporfin release from VISUDYNE® under conditions that replicate in vivo conditions using human serum albumin (HSA). Verteporfin release from the liposomes was quantified using capillary electrophoresis (CE) with optical detection. Verteporfin binding to HSA was quantified by measuring HSA fluorescence that is quenched by drugs binding to specific HSA binding sites. The binding constant of verteporfin to HSA was calculated using the Stern Volmer plot and found to be 1.966 × 10 M at 37 °C. Verteporfin binding to HSA involves one albumin binding site and the binding molar ratio between verteporfin and HSA is approximately 1:1. A rapid partitioning of verteporfin from VISUDYNE® onto HSA takes place within 10 min and involves the release of more than 90% of the verteporfin at physiological temperatures. This study verifies this approach of using CE to rapidly separate liposome and HSA-bound drug, thus minimizing drug release artifacts created with other methods.
维速达尔（VISUDYNE®）是一种维替泊芬脂质体制剂，通过静脉给药用于年龄相关性黄斑变性的光动力治疗。在本研究中，我们开发了一种新的体外方法，使用人血清白蛋白（HSA）在模拟体内条件下定量维速达尔（VISUDYNE®）中维替泊芬的释放。脂质体中维替泊芬的释放通过带光学检测的毛细管电泳（CE）进行定量。维替泊芬与HSA的结合通过测量与特定HSA结合位点结合的药物淬灭的HSA荧光来定量。使用斯特恩-沃尔默图计算维替泊芬与HSA的结合常数，发现在37°C时为1.966×10 M。维替泊芬与HSA的结合涉及一个白蛋白结合位点，维替泊芬与HSA之间的结合摩尔比约为1:1。维替泊芬在10分钟内从维速达尔（VISUDYNE®）快速分配到HSA上，在生理温度下涉及释放超过90%的维替泊芬。本研究验证了使用CE快速分离脂质体和HSA结合药物的这种方法，从而最大限度地减少了其他方法产生的药物释放假象。
