June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Intra-Vitreal Delivery of Interferon Gamma Using Porous Silicon for Treatment of Age-Related Macular Degeneration (AMD).
Author Affiliations & Notes
  • Shachi Saluja
    IITB-Monash Research Academy, Mumbai, Maharashtra, India
  • Lars Esser
    Commonwealth Scientific and Industrial Research Organisation, Melbourne, Victoria, Australia
  • Mark Richardson
    Commonwealth Scientific and Industrial Research Organisation, Melbourne, Victoria, Australia
  • Jayesh Bellare
    Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra, India
  • Nicolas H Voelcker
    Materials Science and Engineering, Monash University, Clayton, Victoria, Australia
    Monash Institute of Pharmaceutical Sciences, Monash University, Clayton, Victoria, Australia
  • Footnotes
    Commercial Relationships   Shachi Saluja, None; Lars Esser, None; Mark Richardson, None; Jayesh Bellare, None; Nicolas Voelcker, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 213. doi:
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      Shachi Saluja, Lars Esser, Mark Richardson, Jayesh Bellare, Nicolas H Voelcker; Intra-Vitreal Delivery of Interferon Gamma Using Porous Silicon for Treatment of Age-Related Macular Degeneration (AMD).. Invest. Ophthalmol. Vis. Sci. 2021;62(8):213.

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

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Abstract

Purpose : Sub-retinal fibrosis remains a challenge to vision even after administering optimal treatments for AMD. Here, we propose porous silicon microparticles (pSiMPs) as reservoir of interferon gamma (IFNγ)-an antifibrotic cytokine, that allow slow release for >30 days minimising rapid clearance and low bioavailability in the eye. Using experimental models, we show that single injection of pSiMPs loaded with IFNγ (pSiMPs- IFNγ) into the vitreous may suffice to adequately treat AMD.

Methods : The pSiMPs were prepared from standard silicon wafer etching using electrochemical anodization in HF/ ethanol mixtures, followed by ultrasonic fracturing. Microparticles were size excluded and characterised using scanning electron microscopy (SEM).
The pSiMP surface was subjected to 1-allyl-2,3-isopropylidine glycerol hydrosilylation to add an active aldehyde moiety to enhance protein binding. WST cell proliferation assay was used to establish the biocompatibility of these pSiMPs.
Transforming growth factor-beta (TGF-β) was used to induce fibrosis in ARPE 19 cells. After 14 days of TGF-β exposure, the cells were treated with pSiMPs- IFNγ. Cell extracts were collected at 7-day interval up to four weeks and their collagen content (indicator of fibrosis) was evaluated using western blot and Sirius red-fast green (RG) staining. Further, we are evaluating our reservoir system in retinal mimics developed using human mesenchymal stem cells and CNV rat model to explore its preclinical potential.

Results : The average particle size characterized by SEM imaging was 20.5±7µm. FTIR-ATR confirmed the addition of aldehyde group to the pSiMPs. The WST assay confirmed that the cells were viable on incubation with pSiMPs up to 96 hours.
The collagen content increased on addition of TGF-β. On addition of pSiMPs- IFNγ, the collagen content decreased steadily over four weeks. Polarised microscopy imaging of RG staining of cells confirmed these results. Total collagen content evaluation reassured a similar pattern indicating that IFNγ is continually released from the pSiMPs.

Conclusions : Through this study, we have demonstrated that the pSiMPs can be used as a reservoir system for sustained intravitreal delivery of IFNγ to reduce fibrosis in AMD. This system can be extended to other eye conditions where posterior segment delivery of therapeutics is limited.

This is a 2021 ARVO Annual Meeting abstract.

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