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Medicine Matters Home Article of the Week Long-acting injectable atovaquone nanomedicines for malaria prophylaxis

Long-acting injectable atovaquone nanomedicines for malaria prophylaxis

ARTICLE: Long-acting injectable atovaquone nanomedicines for malaria prophylaxis

AUTHORS: Rahul P. Bakshi, Lee M. Tatham, Alison C. Savage, Abhai K. Tripathi, Godfree Mlambo, Matthew M. IppolitoElizabeth Nenortas, Steve P. Rannard, Andrew Owen and Theresa A. Shapiro

JOURNAL: Nat Commun. 2018 Jan 22;9(1):315. doi: 10.1038/s41467-017-02603-z.


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-actinginjectable formulations as a new approach for malaria prophylaxis in travellers and for malaria control in the field.

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Kelsey Bennett