TY - JOUR
T1 - Topical siRNA delivery to the cornea and anterior eye by hybrid silicon-lipid nanoparticles
AU - Baran-Rachwalska, Paulina
AU - Torabi-Pour, Nissim
AU - Sutera, Flavia Maria
AU - Ahmed, Mukhtar
AU - Thomas, Keith
AU - Nesbit, M. Andrew
AU - Welsh, Michael
AU - Moore, Tara C. B.
AU - Saffie-Siebert, Suzanne R.
PY - 2020/10/10
Y1 - 2020/10/10
N2 - 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.
AB - 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.
KW - Cornea
KW - Drug delivery
KW - Gene therapy
KW - Nanoparticles
KW - Ocular
KW - ProSilic
KW - Silicon
KW - Topical
KW - siRNA
UR - https://pure.ulster.ac.uk/en/publications/topical-sirna-delivery-to-the-cornea-and-anterior-eye-by-hybrid-s
UR - http://www.scopus.com/inward/record.url?scp=85088109760&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2020.07.004
DO - 10.1016/j.jconrel.2020.07.004
M3 - Article
C2 - 32653503
VL - 326
SP - 192
EP - 202
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -