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Hanaa H. Almogbil, Fadi P. Nasrallah, Vesna Zderic; Feasibility of Therapeutic Ultrasound Application in Topical Scleral Delivery of Avastin. Trans. Vis. Sci. Tech. 2021;10(14):2. doi: https://doi.org/10.1167/tvst.10.14.2.
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Macromolecules have been shown to be effective in vision-saving treatments for various ocular diseases, such as age-related macular degeneration and diabetic retinopathy. The current delivery of macromolecules requires frequent intraocular injections and carries a risk of serious adverse effects.
We tested the application of therapeutic ultrasound as a minimally invasive approach for the delivery of Avastin into the diseased regions of the eye. Avastin (bevacizumab) is an anti-vascular endothelial growth factor (VEGF) antibody with a molecular weight of 149 kDa. We tested the effectiveness and safety of Avastin delivery through rabbit sclera in vitro using a standard diffusion cell model. Ultrasound at frequencies of 400 kHz or 3 MHz with an intensity of 1 W/cm2 was applied for the first 5 minutes of 1-hour drug exposure. Sham treatments mimicked the ultrasound treatments, but ultrasound was not turned on. Absorbance measurements of the receiver compartment solution were performed at 280 nm using a spectrophotometer.
Absorbance measurements indicated no statistical difference between the sham (n = 13) and 400 kHz ultrasound group (n = 15) in the delivery of Avastin through the sclera. However, the absorbance values were statistically different (P < 0.01) between the 3 MHz ultrasound group (0.004, n = 8) and the matched sham group (0.002, n = 7). There was 2.3 times increase in drug delivery in the 3 MHz ultrasound when compared to the corresponding sham group. Histological studies indicated no significant damage in the ultrasound-treated sclera due to ultrasound application.
Our preliminary results provided support that therapeutic ultrasound may be effective in the delivery of Avastin through the sclera.
Our study offers clinical potential for a minimally invasive retinopathy treatment.
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