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Solubilized ubiquinol for preserving corneal function.

Youssef W Naguib1, Sanjib Saha2, Jessica M Skeie3

  • 1Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, 52242, USA; Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt; Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Manufacturing, Deraya University, New Minia City, Minia, 61768, Egypt.

Biomaterials
|June 4, 2021
PubMed
Summary
This summary is machine-generated.

A novel ubiquinol and gamma cyclodextrin (γ-CD) complex improves corneal endothelial cell survival by reducing oxidative stress. This stable, aqueous formulation enhances ROS scavenging and protects against cell death in ophthalmic applications.

Keywords:
Coenzyme Q10Corneal endotheliumCyclodextrinEye bankingFerroptosisInclusion complexKeratoplastyMolecular dockingReactive oxygen speciesUbiquinol

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Area of Science:

  • Ophthalmology
  • Cell Biology
  • Biochemistry

Background:

  • Hypothermic preservation of donor tissues impairs cellular metabolism and mitochondrial function, leading to cell death and reduced graft survival.
  • Reactive oxygen species (ROS) accumulation during hypothermia causes oxidative stress, a major factor in pre-transplant cell death and post-transplant graft failure.
  • Ubiquinol, an active antioxidant form of coenzyme Q10, enhances mitochondrial function and reduces apoptosis in corneal endothelial cells, but its lipophilicity necessitates aqueous formulation.

Purpose of the Study:

  • To develop a stable, aqueous formulation of ubiquinol for ophthalmic use.
  • To assess the efficacy of a ubiquinol-gamma cyclodextrin (γ-CD) complex in protecting corneal endothelial cells from oxidative stress and cell death.
  • To evaluate the transcorneal delivery and retention of ubiquinol using the γ-CD complex.

Main Methods:

  • Complexation of ubiquinol with gamma cyclodextrin (γ-CD) and assessment of binding affinity via docking studies.
  • Evaluation of ubiquinol/γ-CD complex stability in various ophthalmic solutions and its ROS scavenging activity in cell models.
  • Assessment of ubiquinol/γ-CD complex's ability to inhibit lipid peroxidation, protect against ferroptosis, and its transcorneal penetrance in porcine and human donor corneas.

Main Results:

  • γ-CD demonstrated the strongest binding affinity with ubiquinol compared to other cyclodextrins.
  • The ubiquinol/γ-CD complex exhibited enhanced stability in ophthalmic products and superior ROS scavenging activity at lower concentrations compared to free ubiquinol.
  • The complex effectively protected corneal endothelial cells against oxidative damage, lipid peroxidation, and ferroptosis, with demonstrated transcorneal penetrance and improved endothelial retention.

Conclusions:

  • A stable, aqueous ubiquinol/γ-CD complex formulation is suitable for ophthalmic applications.
  • This formulation effectively scavenges ROS and protects corneal endothelial cells from oxidative damage, improving their viability.
  • The γ-CD complex facilitates enhanced corneal penetration and retention of ubiquinol, offering a promising therapeutic strategy for corneal preservation and transplantation.