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Long-acting injectable atovaquone nanomedicines for malaria prophylaxis

Author

Listed:
  • Rahul P. Bakshi

    (The Johns Hopkins University
    The Johns Hopkins Malaria Research Institute)

  • Lee M. Tatham

    (University of Liverpool)

  • Alison C. Savage

    (University of Liverpool)

  • Abhai K. Tripathi

    (The Johns Hopkins Malaria Research Institute
    The Johns Hopkins University)

  • Godfree Mlambo

    (The Johns Hopkins Malaria Research Institute
    The Johns Hopkins University)

  • Matthew M. Ippolito

    (The Johns Hopkins University
    The Johns Hopkins Malaria Research Institute
    The Johns Hopkins University)

  • Elizabeth Nenortas

    (The Johns Hopkins University
    The Johns Hopkins Malaria Research Institute)

  • Steve P. Rannard

    (University of Liverpool)

  • Andrew Owen

    (University of Liverpool)

  • Theresa A. Shapiro

    (The Johns Hopkins University
    The Johns Hopkins Malaria Research Institute
    The Johns Hopkins University)

Abstract

Chemoprophylaxis is currently the best available prevention from malaria, but its efficacy is compromised by non-adherence to medication. Here we develop a long-acting injectable formulation of atovaquone solid drug nanoparticles that confers long-lived prophylaxis against Plasmodium berghei ANKA malaria in C57BL/6 mice. Protection is obtained at plasma concentrations above 200 ng ml-1 and is causal, attributable to drug activity against liver stage parasites. Parasites that appear after subtherapeutic doses remain atovaquone-sensitive. Pharmacokinetic–pharmacodynamic analysis indicates protection can translate to humans at clinically achievable and safe drug concentrations, potentially offering protection for at least 1 month after a single administration. These findings support the use of long-acting injectable formulations as a new approach for malaria prophylaxis in travellers and for malaria control in the field.

Suggested Citation

  • Rahul P. Bakshi & Lee M. Tatham & Alison C. Savage & Abhai K. Tripathi & Godfree Mlambo & Matthew M. Ippolito & Elizabeth Nenortas & Steve P. Rannard & Andrew Owen & Theresa A. Shapiro, 2018. "Long-acting injectable atovaquone nanomedicines for malaria prophylaxis," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02603-z
    DOI: 10.1038/s41467-017-02603-z
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    Cited by:

    1. Victoria A. Balta & Deborah Stiffler & Abeer Sayeed & Abhai K. Tripathi & Rubayet Elahi & Godfree Mlambo & Rahul P. Bakshi & Amanda G. Dziedzic & Anne E. Jedlicka & Elizabeth Nenortas & Keyla Romero-R, 2023. "Clinically relevant atovaquone-resistant human malaria parasites fail to transmit by mosquito," Nature Communications, Nature, vol. 14(1), pages 1-9, December.

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