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Semi-solid prodrug nanoparticles for long-acting delivery of water-soluble antiretroviral drugs within combination HIV therapies

Author

Listed:
  • James J. Hobson

    (University of Liverpool)

  • Amer Al-khouja

    (The Johns Hopkins University School of Medicine)

  • Paul Curley

    (University of Liverpool)

  • David Meyers

    (The Johns Hopkins University School of Medicine)

  • Charles Flexner

    (The Johns Hopkins University School of Medicine
    The Johns Hopkins University School of Medicine)

  • Marco Siccardi

    (University of Liverpool)

  • Andrew Owen

    (University of Liverpool)

  • Caren Freel Meyers

    (The Johns Hopkins University School of Medicine)

  • Steve P. Rannard

    (University of Liverpool)

Abstract

The increasing global prevalence of human immunodeficiency virus (HIV) is estimated at 36.7 million people currently infected. Lifelong antiretroviral (ARV) drug combination dosing allows management as a chronic condition by suppressing circulating viral load to allow for a near-normal life; however, the daily burden of oral administration may lead to non-adherence and drug resistance development. Long-acting (LA) depot injections of nanomilled poorly water-soluble ARVs have shown highly promising clinical results with drug exposure largely maintained over months after a single injection. ARV oral combinations rely on water-soluble backbone drugs which are not compatible with nanomilling. Here, we evaluate a unique prodrug/nanoparticle formation strategy to facilitate semi-solid prodrug nanoparticles (SSPNs) of the highly water-soluble nucleoside reverse transcriptase inhibitor (NRTI) emtricitabine (FTC), and injectable aqueous nanodispersions; in vitro to in vivo extrapolation (IVIVE) modelling predicts sustained prodrug release, with activation in relevant biological environments, representing a first step towards complete injectable LA regimens containing NRTIs.

Suggested Citation

  • James J. Hobson & Amer Al-khouja & Paul Curley & David Meyers & Charles Flexner & Marco Siccardi & Andrew Owen & Caren Freel Meyers & Steve P. Rannard, 2019. "Semi-solid prodrug nanoparticles for long-acting delivery of water-soluble antiretroviral drugs within combination HIV therapies," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09354-z
    DOI: 10.1038/s41467-019-09354-z
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