Long-acting injectable atovaquone nanomedicines for malaria prophylaxis



Bakshi, Rahul P, Tatham, Lee M ORCID: 0000-0001-9448-8876, Savage, Alison C ORCID: 0000-0002-5312-9946, Tripathi, Abhai K, Mlambo, Godfree, Ippolito, Matthew M, Nenortas, Elizabeth, Rannard, SP ORCID: 0000-0002-6946-1097, Owen, Andrew ORCID: 0000-0002-9819-7651 and Shapiro, Theresa A
(2018) Long-acting injectable atovaquone nanomedicines for malaria prophylaxis. Nature Communications, 9.

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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.

Item Type: Article
Uncontrolled Keywords: Drug delivery, Malaria
Depositing User: Symplectic Admin
Date Deposited: 25 Jan 2018 10:27
Last Modified: 15 Oct 2021 03:10
DOI: 10.1038/s41467-017-02603-z
Open Access URL: https://www.nature.com/articles/s41467-017-02603-z
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3016829