Long-acting injectable atovaquone nanomedicines for malaria prophylaxis

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 ma...

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Bibliographic Details
Published inNature communications Vol. 9; no. 1; pp. 315 - 8
Main Authors Bakshi, Rahul P, Tatham, Lee M, Savage, Alison C, Tripathi, Abhai K, Mlambo, Godfree, Ippolito, Matthew M, Nenortas, Elizabeth, Rannard, Steve P, Owen, Andrew, Shapiro, Theresa A
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 22.01.2018
Nature Publishing Group UK
Nature Portfolio
Subjects
Animals
Anopheles - parasitology
Antimalarials - therapeutic use
Atovaquone
Atovaquone - blood
Atovaquone - therapeutic use
Chemoprevention - methods
Disease Models, Animal
Drug Carriers - therapeutic use
Drug Resistance - genetics
Drugs
Female
Formulations
Humans
Liver
Malaria
Malaria - drug therapy
Malaria - prevention & control
Male
Mice
Mice, Inbred C57BL
Nanoparticles
Nanoparticles - therapeutic use
Parasites
Pharmacodynamics
Pharmacology
Plasmodium berghei - drug effects
Prophylaxis
Theranostic Nanomedicine
Travellers
Vector-borne diseases
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Summary: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 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.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-017-02603-z