title: Sulfobutyl ether β-cyclodextrin (Captisol(®) ) and methyl β-cyclodextrin enhance and stabilize fluorescence of aqueous indocyanine green.
abstract: As the only FDA-approved near-infrared fluorophore, indocyanine green (ICG) is commonly used to image vasculature in vivo. ICG degrades rapidly in solution, which limits its usefulness in certain applications, including time-sensitive surgical procedures. We propose formulations that address this shortcoming via complexation with β-cyclodextrin derivatives (β-CyD), which are known to create stabilizing inclusion complexes with hydrophobic molecules. Here, we complexed ICG with highly soluble methyl β-CyD and FDA-approved sulfobutyl ether β-CyD (Captisol(®) ) in aqueous solution. We measured the fluorescence of the complexes over 24 h. We found that both CyD+ICG complexes exhibit sustained fluorescence increases of >2.0× versus ICG in water and >20.0× in PBS. Using transmission electron microscopy, we found evidence of reduced aggregation in complexes versus ICG alone. We thus conclude that this reduction in aggregation helps mitigate fluorescence autoquenching of CyD+ICG complexes compared in ICG alone. We also found that while ICG complexed with methyl β-CyD severely reduced the viability of MRC-5 fibroblasts, ICG complexed with sulfobutyl ether β-CyD had no effect on viability. These results represent an important first step toward enhancing the utility of aqueous ICG by reducing aggregation-dependent fluorescence degradation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1457-1464, 2016.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, 11794-5281.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DeDora
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, 11794-5281.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Suhrland
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, 11794-5281.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Goenka
authors.affiliation: Department of Biochemistry and Cellular Biology, Stony Brook University, Stony Brook, New York, 11794-5281.
authors.forename: Sayan
authors.initials: S
authors.lastname: Mullick Chowdhury
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, 11794-5281.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Lalwani
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, 11794-5281.
authors.forename: Lilianne R
authors.initials: LR
authors.lastname: Mujica-Parodi
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, 11794-5281. balaji.sitharaman@stonybrook.edu.
authors.forename: Balaji
authors.initials: B
authors.lastname: Sitharaman
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005453:Fluorescence; D007208:Indocyanine Green / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C093196:SBE4-beta-cyclodextrin; D007208:Indocyanine Green
keywords: cyclodextrin; fluorescence; inclusion complex; indocyanine green; vascular imaging