June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Biodegradable silicon nanoneedles for sustained treatment of angiogenesis
Author Affiliations & Notes
  • Yannis Mantas Paulus
    Ophthalmology and Visual Sciences, Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States
  • Woohyun Park
    School of Mechanical Engineering, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States
  • Van Phuc Nguyen
    Ophthalmology and Visual Sciences, Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States
  • Chi Hwan Lee
    School of Mechanical Engineering, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States
  • Footnotes
    Commercial Relationships   Yannis Paulus Iridex, Code C (Consultant/Contractor), Hedgefog Research Inc, Code C (Consultant/Contractor), Putnam Associated Consulting, Code C (Consultant/Contractor), PhotoSonoX LLC, Code O (Owner), EyeSonics LLC, Code O (Owner), Paulus Enterprises LLC, Code O (Owner), PhotoSonoX LLC, University of Michigan,, Code P (Patent); Woohyun Park None; Van Phuc Nguyen None; Chi Hwan Lee Purdue University, Code P (Patent)
  • Footnotes
    Support  NIH Grant 1R01EY033000, NIH Grant 1R41EY031219, NIH Grant 5K08EY027458
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1857. doi:
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      Yannis Mantas Paulus, Woohyun Park, Van Phuc Nguyen, Chi Hwan Lee; Biodegradable silicon nanoneedles for sustained treatment of angiogenesis. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1857.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Angiogenesis is a major cause of vision loss and blindness in numerous ocular diseases, including in the cornea, macular degeneration, and diabetes. To treat angiogenesis, laser photocoagulation, photodynamic therapy, and anti-vascular endothelial growth factor therapy such as bevacizumab (BEV) are often utilized, but these treatments can damage adjacent healthy tissue or require frequent administration and can carry a risk of infection. To improve the treatment efficiency, increase the treatment duration, and reduce these side-effects, the current study describes a novel treatment of ocular angiogenesis using miniature biodegradable silicon nanoneedles (SiNNs) fabricated on a tear-soluble contact lens.

Methods : The SiNNs were encapsulated with BEV (BEV@SiNNs) and used as drug carriers for long-term, sustained drug delivery. The potential treatment effects of BEV@SiNNs were evaluated on a rabbit corneal neovascularization (CNV) model (n = 24) after approval from the University of Michigan IACUC. To generate CNV, a suture was placed on the animal cornea and allowed for CNV development up to one month. BEV@SiNNs were applied on the cornea and monitored by optical coherence tomography (OCT), color photography, and red-free imaging. The treatment outcome was followed up for one-month post-treatment.

Results : The tear-soluble contact lens dissolved within 1 minute. CNV was rapidly reduced within 7 days post-treatment that persisted to at least 28 days (Figure) whereas no CNV reduction occurred with control. Vessel density was 2.9 ± 2.0% for BEV@SiNNs versus 85.8 ± 0.9% for control. SiNNs did not cause cytotoxicity. Histological images showed normal corneal morphology without evidence of cell death or damage to the corneal endothelium cells, corneal thickness, and limbal stem cells.

Conclusions : The SiNNs are an efficient drug delivery vehicle for treatment of ocular angiogenesis.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

In vivo imaging of corneal neovascularization treated with bevacizumab encapsulated silicon nanoneedles: (a) Color, red-free, segmented and overlay image of corneal neovascularization (CNV) before treatment. (b) CNV after treatment at day 28 demonstrating near resolution of CNV. (c) B-scan OCT before treatment, (d) OCT image after inserted water soluble contact lens. (e) OCT at day 28 post treatment. (f-g) H&E staining of endothelial cells of control (f) and treatment group (g). The density of endothelial cells was not changed.

In vivo imaging of corneal neovascularization treated with bevacizumab encapsulated silicon nanoneedles: (a) Color, red-free, segmented and overlay image of corneal neovascularization (CNV) before treatment. (b) CNV after treatment at day 28 demonstrating near resolution of CNV. (c) B-scan OCT before treatment, (d) OCT image after inserted water soluble contact lens. (e) OCT at day 28 post treatment. (f-g) H&E staining of endothelial cells of control (f) and treatment group (g). The density of endothelial cells was not changed.

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