Development of Moderate Intensity Focused Ultrasound (MIFU) for Ocular Drug Delivery

Alejandra Gonzalez-Calle; Runze Li; Isaac Asante; Juan Carlos Martinez-Camarillo; Stan Louie; Qifa Zhou; Mark S Humayun

doi:10.34133/2022/9840678

Development of Moderate Intensity Focused Ultrasound (MIFU) for Ocular Drug Delivery

BME Front. 2022 Jun 8:2022:9840678. doi: 10.34133/2022/9840678. eCollection 2022.

Authors

Alejandra Gonzalez-Calle^#^{1

2}, Runze Li^#³, Isaac Asante^{1

2

4}, Juan Carlos Martinez-Camarillo^{1

2}, Stan Louie^{1

2

4}, Qifa Zhou^{1

2

3}, Mark S Humayun^{1

2

3}

Affiliations

¹ USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles California, USA.
² USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles California, USA.
³ Department of Biomedical Engineering, University of Southern California, Los Angeles California, USA.
⁴ USC School of Pharmacy, University of Southern California, Los Angeles California, USA.

^# Contributed equally.

Abstract

The purpose of this study is to develop a method for delivering antiinflammatory agents of high molecular weight (e.g., Avastin) into the posterior segment that does not require injections into the eye (i.e., intravitreal injections; IVT). Diseases affecting the posterior segment of the eye are currently treated with monthly to bimonthly intravitreal injections, which can predispose patients to severe albeit rare complications like endophthalmitis, retinal detachment, traumatic cataract, and/or increased intraocular. In this study, we show that one time moderate intensity focused ultrasound (MIFU) treatment can facilitate the penetration of large molecules across the scleral barrier, showing promising evidence that this is a viable method to deliver high molecular weight medications not invasively. To validate the efficacy of the drug delivery system, IVT injections of vascular endothelial growth factor (VEGF) were used to create an animal model of retinopathy. The creation of this model allowed us to test anti-VEGF medications and evaluate the efficacy of the treatment. In vivo testing showed that animals treated with our MIFU device improved on the retinal tortuosity and clinical dilation compared to the control group while evaluating fluorescein angiogram (FA) Images.