Journal
PHARMACEUTICAL RESEARCH
Volume 27, Issue 9, Pages 1900-1913Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-010-0190-y
Keywords
indocyanine green; thermo-sensitivity; micelle; stability; near-infrared tumor imaging
Funding
- Washington Technology Center
- Omeros Corporation
- National Institutes of Health [R01 CA120480-Li]
- Washington State Life Sciences Discovery Fund [2496490]
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [0940321] Funding Source: National Science Foundation
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Purpose Indocyanine green (ICG), an FDA-approved near infrared (NIR) dye, has potential application as a contrast agent for tumor detection. Because ICG binds strongly to plasma proteins and exhibits aqueous, photo, and thermal instability, its current applications are largely limited to monitoring blood flow. To address these issues, ICG was encapsulated and stabilized within polymeric micelles formed from the thermo-sensitive block copolymer Pluronic F-127, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), to increase the stability and circulation time of ICG. Methods ICG-loaded Pluronic micelles were prepared at various concentrations of Pluronic and ICG and characterized by determining particle sizes, dye loading efficiency, and the kinetics of dye degradation. Forster resonance energy transfer spectroscopy was employed to monitor the stability of Pluronic micelles in physiological solutions. The plasma clearance kinetics and biodistribution of ICG-loaded micelles was also determined after intravenous delivery to CT-26 colon carcinoma tumor-bearing mice, and NIR whole-body imaging was performed for tumor detection. Results The Pluronic F-127 micelles showed efficient ICG loading, small size, stabilized ICG fluorescence, and prolonged circulation in vivo. Solid tumors in mice were specifically visualized after intravenous administration of ICG-loaded micelles. Conclusions These materials are therefore promising formulations for noninvasive NIR tumor imaging applications.
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