Profiling in-vitro release of verteporfin from VISUDYNE® liposomal formulation and investigating verteporfin binding to human serum albumin

Abstract

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 × 107 M−1 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.