Dextran Microgels for Time-Controlled Delivery of siRNA

Authors

  • Koen Raemdonck,

    1. Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics Faculty of Pharmaceutical Sciences, Ghent University Harelbekestraat 72, 9000 Ghent (Belgium)
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  • Tinneke G. Van Thienen,

    1. Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics Faculty of Pharmaceutical Sciences, Ghent University Harelbekestraat 72, 9000 Ghent (Belgium)
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  • Roosmarijn E. Vandenbroucke,

    1. Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics Faculty of Pharmaceutical Sciences, Ghent University Harelbekestraat 72, 9000 Ghent (Belgium)
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  • Niek N. Sanders,

    1. Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics Faculty of Pharmaceutical Sciences, Ghent University Harelbekestraat 72, 9000 Ghent (Belgium)
    2. Laboratory of Veterinary Gene Therapy, Department of Nutrition, Genetics and Ethology Faculty of Veterinary Medicine, Ghent University Heidestraat 19, 9820 Merelbeke (Belgium)
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  • Joseph Demeester,

    1. Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics Faculty of Pharmaceutical Sciences, Ghent University Harelbekestraat 72, 9000 Ghent (Belgium)
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  • Stefaan C. De Smedt

    Corresponding author
    1. Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics Faculty of Pharmaceutical Sciences, Ghent University Harelbekestraat 72, 9000 Ghent (Belgium)
    • Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics Faculty of Pharmaceutical Sciences, Ghent University Harelbekestraat 72, 9000 Ghent (Belgium).
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  • K. Raemdonck is a doctoral fellow of the IWT (Institute for the Promotion of Innovation through Science and Technology in Flanders). Dr. N. Sanders is a postdoctoral fellow of FWO-Flanders (Fund for Scientific Research-Flanders). Financial support is acknowledged with gratitude. Dr. K. Braeckmans is thanked for his help with size distribution measurements. Olivier Janssens and Karel Lambert are acknowledged for conducting the SEM and AFM measurements, respectively. The EU (FP6) is acknowledged for financially supporting MEDITRANS, an Integrated Project on targeted delivery of nanomedicine. Supporting Information is available online from Wiley InterScience or from the author.

Abstract

To apply siRNA as a therapeutic agent, appropriate attention should be paid to the optimization of the siRNA gene silencing effect, both in terms of magnitude and duration. Intracellular time-controlled siRNA delivery could aid in tailoring the kinetics of siRNA gene knockdown. However, materials with easily tunable siRNA release properties have not been subjected to thorough investigation thus far. This report describes cationic biodegradable dextran microgels which can be loaded with siRNA posterior to gel formation. Even though the siRNAs are incorporated in the hydrogel network based on electrostatic interaction, still a time-controlled release can be achieved by varying the initial network density of the microgels. To demonstrate the biological functionality of the siRNA loaded gels, we studied their cellular internalization and enhanced green fluorescent protein (EGFP) gene silencing potential in HUH7 human hepatoma cells.

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