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Sustained Zero-Order Release of Intact Ultra-Stable Drug-Loaded Liposomes from an Implantable Nanochannel Delivery System

Authors

  • Christian Celia,

    1. Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave. Houston, TX 77030, USA
    2. Department of Health Sciences, University “Magna Graecia” of Catanzaro, V.le “S. Venuta” Germaneto–Catanzaro 88100, Italy
    Current affiliation:
    1. C. C. and S. F. contributed equally to this work.
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  • Silvia Ferrati,

    1. Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave. Houston, TX 77030, USA
    Current affiliation:
    1. C. C. and S. F. contributed equally to this work.
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  • Shyam Bansal,

    1. Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave. Houston, TX 77030, USA
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  • Anne L. van de Ven,

    1. Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave. Houston, TX 77030, USA
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  • Barbara Ruozi,

    1. Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena 41100, Italy
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  • Erika Zabre,

    1. Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave. Houston, TX 77030, USA
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  • Sharath Hosali,

    1. NanoMedical Systems, Inc, 2706 Montopolis Drive, Austin, TX 78741, USA
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  • Donatella Paolino,

    1. Department of Health Sciences, University “Magna Graecia” of Catanzaro, V.le “S. Venuta” Germaneto–Catanzaro 88100, Italy
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  • Maria Grazia Sarpietro,

    1. Department of Drug Sciences, University of Catania, V.le A. Doria 6, Catania 95125, Italy
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  • Daniel Fine,

    1. Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave. Houston, TX 77030, USA
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  • Massimo Fresta,

    1. Department of Health Sciences, University “Magna Graecia” of Catanzaro, V.le “S. Venuta” Germaneto–Catanzaro 88100, Italy
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  • Mauro Ferrari,

    1. Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave. Houston, TX 77030, USA
    2. Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 1006, USA
    3. Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX 77251, USA
    4. Alliance for NanoHealth, 6670 Bertner Ave., Houston, TX 77030, USA
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  • Alessandro Grattoni

    Corresponding author
    1. Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave. Houston, TX 77030, USA
    • Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave. Houston, TX 77030, USA.

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Abstract

Metronomic chemotherapy supports the idea that long-term, sustained, constant administration of chemotherapeutics, currently not achievable, could be effective against numerous cancers. Particularly appealing are liposomal formulations, used to solubilize hydrophobic therapeutics and minimize side effects, while extending drug circulation time and enabling passive targeting. As liposome alone cannot survive in circulation beyond 48 h, sustaining their constant plasma level for many days is a challenge. To address this, we develop, as a proof of concept, an implantable nanochannel delivery system and ultra-stable PEGylated lapatinib-loaded liposomes, and we demonstrate the release of intact vesicles for over 18 d. Further, we investigate intravasation kinetics of subcutaneously delivered liposomes and verify their biological activity post nanochannel release on BT474 breast cancer cells. The key innovation of this work is the combination of two nanotechnologies to exploit the synergistic effect of liposomes, demonstrated as passive-targeting vectors and nanofluidics to maintain therapeutic constant plasma levels. In principle, this approach could maximize efficacy of metronomic treatments.

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