June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Ubiquinol loaded targeted nanoparticles for Fuchs endothelial corneal dystrophy
Author Affiliations & Notes
  • Sanjib Saha
    Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, Iowa, United States
  • Jessica M. Skeie
    Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States
    Iowa Lions Eye Bank, Iowa City, Iowa, United States
  • Megan Polz
    Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, Iowa, United States
  • Hanna Shevalye
    Iowa Lions Eye Bank, Iowa City, Iowa, United States
  • Tim Eggleston
    Iowa Lions Eye Bank, Iowa City, Iowa, United States
  • Apurva Dusane
    Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, Iowa, United States
  • Pornpoj Phruttiwanichakun
    Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, Iowa, United States
  • Esraa Mohamed
    Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, Iowa, United States
  • Greg Schmidt
    Iowa Lions Eye Bank, Iowa City, Iowa, United States
  • Mark A Greiner
    Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States
    Iowa Lions Eye Bank, Iowa City, Iowa, United States
  • Aliasger K. Salem
    Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, Iowa, United States
  • Footnotes
    Commercial Relationships   Sanjib Saha S5G Therapeutics Inc., Code O (Owner); Jessica Skeie S5G Therapeutics Inc., Code O (Owner); Megan Polz None; Hanna Shevalye None; Tim Eggleston None; Apurva Dusane None; Pornpoj Phruttiwanichakun None; Esraa Mohamed None; Greg Schmidt S5G Therapeutics Inc., Code O (Owner); Mark Greiner S5G Therapeutics Inc., Code O (Owner); Aliasger Salem S5G Therapeutics Inc., Code O (Owner)
  • Footnotes
    Support   None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1335. doi:
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    • Get Citation

      Sanjib Saha, Jessica M. Skeie, Megan Polz, Hanna Shevalye, Tim Eggleston, Apurva Dusane, Pornpoj Phruttiwanichakun, Esraa Mohamed, Greg Schmidt, Mark A Greiner, Aliasger K. Salem; Ubiquinol loaded targeted nanoparticles for Fuchs endothelial corneal dystrophy. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1335.

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

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Abstract

Purpose : To date, corneal transplantation is the only way to restore vision in advanced cases of Fuchs endothelial corneal dystrophy (FECD). To prevent FECD progression, we aimed to develop ubiquinol loaded, cRGD conjugated, corneal endothelial cell (CEC) targeted PLGA nanoparticles (NPs) as topical eye drops to prevent iron-mediated lipid peroxidation (ferroptosis) in CECs.

Methods : The presence of αvβ3 receptor on immortalized cultured FECD CECs (F35T; n=3) was detected by flow cytometry. PLGA-PEG-COOH copolymer was synthesized by EDC-NHS chemistry. Ubiquinol loaded NPs were prepared by nanoprecipitation. NPs were conjugated with cyclo (Arg-Gly-Asp-D-Phe-Lys) peptide (c(RGDfk)) by EDC-NHS crosslinking chemistry. NPs were characterized by measuring size and charge using a Zetasizer. Drug loading and encapsulation efficiency were quantified using HPLC-DAD. Stability of NPs in the aqueous phase using Optisol-GS® corneal storage media was determined up to 21 days at 4°C by LC-MS/MS. The efficacy of NPs to protect F35T cells from RSL3 induced ferroptosis was studied using MTS reagent. Coumarin-6 loaded cRGD conjugated NPs were prepared similarly to study penetration of murine corneas. Efficacy of ubiquinol loaded NPs was tested on mice with a well-characterized FECD mutation (129S6/SvEvTac Col8a2Q455K).

Results : Presence of αvβ3 on F35T cells was confirmed by flow cytometry. 1H-NMR data confirmed conjugation of PLGA with PEG. NPs are characterized by a small size (150.57±4.72 nm) and narrow polydispersity index (0.10±0.005). Ubiquinol loaded NPs showed higher stability compared to free ubiquinol (P<0.01). cRGD conjugated NPs prevented RSL3 induced ferroptosis in F35T CECs and resulted in higher cell viability compared to free ubiquinol (P<0.001). cRGD conjugated NPs showed higher cell viability than non-cRGD NPs, indicating higher cell uptake via αvβ3 receptor (P<0.0001). Topical delivery of coumarin-6 loaded cRGD conjugated NPs showed penetration of the entire murine cornea by 30 min. In FECD mice, the rate of guttae formation over 2 months was lower in cRGD-ubiquinol NP treated mice compared to sham treatment.

Conclusions : Findings indicate the successful development of ubiquinol loaded cRGD conjugated NPs as a targeted drug delivery strategy for CECs to prevent FECD progression. This formulation has the potential to be an effective topical pharmacotherapeutic for the medical treatment of FECD.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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