Stabilization of indocyanine green by encapsulation within micellar systems

Indocyanine green (ICG) is a fluorescence dye that is widely used for near-infrared imaging. Application of this dye is limited by its numerous disadvantageous properties in aqueous solution, including its concentration-dependent aggregation, poor aqueous stability in vitro and low quantum yield. Additionally, ICG is highly bound to nonspecific plasma proteins, leading to rapid elimination from the body with a half-life of 3-4 min. In this study, encapsulation of ICG within various micellar systems was investigated with the aim of overcoming these limitations. The aggregation behavior of different aqueous ICG formulations was studied using cryogenic transmission electron microscopy (cryo-TEM) and absorption spectroscopy. The micellar systems were characterized by their optical properties, particle size distribution, zeta potential and hemolytic activity. Encapsulation efficiency was determined using analytical ultracentrifugation. The best results were achieved for ICG encapsulated within aqueous Solutol HS 15 micelles. This formulation exhibited a lower aggregation behavior, a 3-fold increased quantum yield and high aqueous stability (over 4 weeks) compared to free aqueous ICG. The micelles were found to have an average diameter of 12 nm and a zeta potential close to zero (-2.1 +/- 1.7 mV). Encapsulation efficiency of ICG was high at 95%. The formulation did not display significant hemolytic activity. Consequently, Solutol HS 15 micelles are suitable nanocarriers for ICG which improve the optical properties and stability of the dye.