Flexible Nanosomes (SECosomes) Enable Efficient siRNA Delivery in Cultured Primary Skin Cells and in the Viable Epidermis of Ex Vivo Human Skin

Authors

  • Barbara Geusens,

    1. Department of Dermatology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium
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  • Mireille Van Gele,

    1. Department of Dermatology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium
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  • Sien Braat,

    1. Department of Dermatology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium
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  • Stefaan C. De Smedt,

    1. Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Harelbekestraat 72, B-9000 Ghent, Belgium
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  • Marc C. A. Stuart,

    1. Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
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  • Tarl W. Prow,

    1. Therapeutics Research Centre, Southern Clinical Division, Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Australia
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  • Washington Sanchez,

    1. Therapeutics Research Centre, Southern Clinical Division, Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Australia
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  • Michael S. Roberts,

    1. Therapeutics Research Centre, Southern Clinical Division, Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Australia
    2. School of Pharmacy & Medical Sciences, University of South Australia, North Terrace, Adelaide, Australia
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  • Niek N. Sanders,

    1. Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, B-9820 Merelbeke, Belgium
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  • Jo Lambert

    Corresponding author
    1. Department of Dermatology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium
    • Department of Dermatology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
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Abstract

The extent to which nanoscale-engineered systems cross intact human skin and can exert pharmacological effects in viable epidermis is controversial. This research seeks to develop a new lipid-based nanosome that enables the effective delivery of siRNA into human skin. The major finding is that an ultraflexible siRNA-containing nanosome—prepared using DOTAP, cholesterol, sodium cholate, and 30% ethanol—penetrates into the epidermis of freshly excised intact human skin and is able to enter into the keratinocytes. The nanosomes, called surfactant-ethanol-cholesterol-osomes (SECosomes), show excellent size, surface charge, morphology, deformability, transfection efficiency, stability, and skin penetration capacity after complexation with siRNA. Importantly, these nanosomes have ideal characteristics for siRNA encapsulation, in that the siRNA is stable for at least 4 weeks, they enable highly efficient transfection of in vitro cultured cells, and are shown to transport siRNA delivery through intact human skin where changes in the keratinocyte cell state are demonstrated. It is concluded that increasing flexibility in nanosomes greatly enhances their ability to cross the intact human epidermal membrane and to unload their payload into targeted epidermal cells.

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