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  • CXCL1 gene silencing in skin using liposome-encapsulated siRNA delivered by microprojection array

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    Author(s)
    Haigh, Oscar
    Depelsenaire, Alexandra CI
    Meliga, Stefano C
    Yukiko, Sally R
    McMillan, Nigel AJ
    Frazer, Ian H
    Kendall, Mark AF
    Griffith University Author(s)
    McMillan, Nigel
    Year published
    2014
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    Abstract
    The barrier morphology of skin provides major obstacles for the application of siRNA for gene silencing, which current delivery technologies do not effectively overcome. Emerging technologies utilise microprojection array devices to penetrate into the skin epidermis and dermis for delivery of drug payloads. Delivery of siRNA by such devices has been proven in principle, yet requires optimisation for clinical applications. Herein, we demonstrate the use of Nanopatch頭icroprojection arrays to deliver liposome-encapsulated siRNA to overcome skin barrier, and in vivo siRNA delivery hurdles. This application provided effective ...
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    The barrier morphology of skin provides major obstacles for the application of siRNA for gene silencing, which current delivery technologies do not effectively overcome. Emerging technologies utilise microprojection array devices to penetrate into the skin epidermis and dermis for delivery of drug payloads. Delivery of siRNA by such devices has been proven in principle, yet requires optimisation for clinical applications. Herein, we demonstrate the use of Nanopatch頭icroprojection arrays to deliver liposome-encapsulated siRNA to overcome skin barrier, and in vivo siRNA delivery hurdles. This application provided effective silencing of CXCL1 expression induced by the co-delivery of Fluvax 2012y microprojection array. Liposomes encapsulating siRNA were dry-coated onto microprojection arrays, and remained intact after elution from arrays in vitro. Microprojection arrays facilitated the delivery of fluorescently-labelled nucleic acids through murine ear stratum corneum to the epidermis and dermis, with diffusion from microprojections into adjacent skin evident within 30 s. CXCL1 mRNA, induced by delivery of Fluvax by microprojection array, was reduced by 75% up to 20 h post-treatment by co-delivery of liposome-encapsulated CXCL1-specific siRNA, but not by arrays co-delivering liposome-encapsulated control siRNA. CXCL1 protein expression in explant cultures from skin treated with arrays bearing CXCL1 specific or control siRNA was similarly reduced. These results as a test case have many implications for gene silencing in skin and inflammation, with the benefit of targeted delivery using microprojection arrays to deliver liposome-encapsulated siRNA.
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    Journal Title
    Journal of Controlled Release
    Volume
    194
    DOI
    https://doi.org/10.1016/j.jconrel.2014.08.021
    Copyright Statement
    © 2014 Elsevier B.V. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
    Subject
    Biomedical engineering
    Biomedical engineering not elsewhere classified
    Chemical engineering
    Pharmacology and pharmaceutical sciences
    Publication URI
    http://hdl.handle.net/10072/65672
    Collection
    • Journal articles

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