In Vivo Imaging of a New Indocyanine Green Micelle Formulation in an Animal Model of Laser-Induced Choroidal Neovascularization

Abstract

Micelle formulated ICG can be visualized in the retinal vasculature and laser-induced CNV in vivo and ex vivo. Micellar ICG/HS 15 showed in vivo stronger signal intensity when compared to ICG for all tested dosages. Following further investigations, ICG/HS 15 may be evaluated in patients with retinal and choroidal diseases for more refined diagnosis.

In Vivo Imaging of Fluorescent Probes Linked to Antibodies Against Human and Rat Vascular Endothelial Growth Factor

“…The laser-induced animal model of choroidal neovascularization (CNV) has been extensively used in various preclinical research projects. 14,15 It has been demonstrated that VEGF is upregulated in this model with a peak level of expression between 3 and 7 days following laser application. [16][17][18] Several therapeutic inhibitory antibodies or antibody fragments against VEGF are available but there is an ongoing controversial discussion in the literature about targeting of the humanized monoclonal anti-VEGF antibody bevacizumab to rodent VEGF isoforms.…”

“…Human umbilical vein endothelial cells (HUVEC; PromoCell GmbH, Heidelberg, Germany) were cultured in endothelial cell growth medium with supplement-mix (PromoCell GmbH) as previously described. 15 This study complies with the principles outlined in the Declaration of Helsinki for medical research involving human subjects (2008). Cells were seeded in medium at 2 3 10 4 cells/mL, cultured at 378C with 5% CO 2 up to 80% of confluence, and then split 1:4.…”

“…All investigations were performed on male adult Dark Agouti rats, each weighting 200 to 250 g, and CX 3 CR1 GFP/þ mice (provided by Christian Kurts, University of Bonn, Bonn, Germany), weighting approximately 20 g. Rats were anesthetized for all procedures by intraperitoneal injection of ketamine (60 mg/kg body weight) and medetomidine hydrochloride (0.5 mg/kg body weight). 15 Anesthesia of rats was reversed by intraperitoneal injection of a 20% atipamezol (1 mL/kg) solution. Mice were anesthetized by intraperitoneal injection of a mixture of ketamine (50 mg/kg body weight) and xylazin (5 mg/kg body weight).…”

“…Retinal laser lesions in age-matched rats and mice were placed around the optic nerve head with an argon laser (Novus2000; Coherent, Dieburg, Germany) to induce CNV formation at day 0 (D0) as previously described. 15,26 The following settings were used: 514-nm excitation, 0.1-second pulse duration, 150-mW laser power, and 100-lm spot size for rats as well as 514nm excitation, 0.1-second pulse duration, 200-mW laser power, and 50-lm spot size for laser treatment in mice.…”

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies

“…This led to reduced quenching of the dye and thus generated a more intense fluorescence signal. Therefore, the prepared micellar formulation may be effective in the management of choroidal and potentially also retinal diseases [140]. Chen and co-workers developed a MPEG-PCL based micellar formulation of diclofenac.…”