Topical siRNA delivery to the cornea and anterior eye by hybrid silicon-lipid nanoparticles

Paulina Baran-Rachwalska, Nissim Torabi-Pour, Flavia Maria Sutera, Mukhtar Ahmed, Keith Thomas, M. Andrew Nesbit, Michael Welsh, Tara C. B. Moore, Suzanne R. Saffie-Siebert

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Abstract

The major unmet need and crucial challenge hampering the exciting potential of
RNAi therapeutics in ophthalmology is to find an effective, safe and non-invasive means of delivering siRNA to the cornea. Although all tissues of the eye are accessible by injection, topical application is preferable for the frequent treatment regimen that would be necessary for siRNA-induced gene silencing. However, the ocular surface is one of the more complex biological barriers for drug delivery due to the combined effect of short contact time, tear dilution and poor corneal cell penetration. Using nanotechnology to overcome the challenges, we developed a unique silicon-based delivery platform for ocular delivery of siRNA. This biocompatible hybrid of porous silicon nanoparticles and lipids has demonstrated an ability to bind nucleic acid and deliver functional siRNA to corneal cells both in vitro and in vivo. Potent transfection of human corneal epithelial cells with siRNA-ProSilic® formulation was followed by a successful downregulation of reporter protein expression. Moreover, siRNA complexed with this silicon-based hybrid and applied in vivo topically to mice eyes penetrated across all cornea layers and resulted in a significant reduction of the targeted protein expression in corneal epithelium. In terms of siRNA loading capacity, system versatility, and potency of action, ProSilic provides unique attributes as a biodegradable delivery platform for therapeutic oligonucleotides.
Original languageEnglish
Pages (from-to)192-202
Number of pages11
JournalJournal of Controlled Release
Volume326
Early online date9 Jul 2020
DOIs
Publication statusE-pub ahead of print - 9 Jul 2020

Keywords

  • Cornea
  • Drug delivery
  • Gene therapy
  • Nanoparticles
  • Ocular
  • ProSilic
  • Silicon
  • Topical
  • siRNA

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