Rapid assessment of ocular drug delivery in a novel ex vivo corneal model

Research output: Contribution to journalArticlepeer-review

Authors

  • Thomas Leigh
  • Ella Courtie
  • Richard Moakes
  • Gibran Butt
  • Zubair Ahmed
  • Richard J Blanch

External organisations

  • miRNA Diagnostics
  • Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
  • Institute for Inflammation and Ageing
  • NIHR Surgical Reconstruction and Microbiology Research Centre
  • School of Chemistry, University of Birmingham
  • School of Chemical Engineering
  • Academic Unit of Ophthalmology
  • Inflammatory Eye Disease Service, Birmingham & Midland Eye Centre, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK.
  • Academic Department of Military Surgery and Trauma (ADMST)
  • ROYAL CENTRE FOR DEFENCE MEDICINE
  • Department of Ophthalmology
  • University Hospitals Birmingham NHS Foundation Trust

Abstract

Drug delivery by topical application has higher patient acceptance and lower morbidity than intraocular injection, but many ophthalmic treatments are unable to enter the eye or reach the posterior segment after topical application. The first stage towards posterior segment delivery after topical application is ocular surface penetration and existing models are in vivo or use large quantities of tissue. We therefore developed a novel ex vivo model using discs of porcine and human cornea and sclera (5 mm diameter) to assess penetration of a candidate neuroprotective siRNA. siRNA against caspase 2 or control solutions of known penetrance were applied to the corneal epithelial surface and trans-corneal penetration and corneal adsorbance measured at fixed time points. To demonstrate that leakage did not occur, we applied dextran blue, which should not penetrate the intact cornea and did not do so in our model. Fluorescein penetration (0.09%) was less than rhodamine B (6.98%) at 60 min. siCASP2 penetration was 0.01% by 60 min. When the applied siCASP2 was washed off after 2 min, (representing lacrimal drainage) 0.071% penetrated porcine cornea by 60 min and 0.0002% penetrated human cornea and 0.001% penetrated human sclera. Our ex vivo model rapidly and cost-effectively assesses transcorneal penetration of candidate topical therapies, allowing rates of trans-corneal penetration for potential therapies such as siRNA to be evaluated with small quantities of human or animal tissue.

Details

Original languageEnglish
Pages (from-to)11754
JournalScientific Reports
Volume10
Issue number1
Publication statusPublished - 16 Jul 2020