@article{fc366ab73c0f49e19e7a753a601f6c92,
title = "Long-acting injectable atovaquone nanomedicines for malaria prophylaxis",
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.",
author = "Bakshi, {Rahul P.} and Tatham, {Lee M.} and Savage, {Alison C.} and Tripathi, {Abhai K.} and Godfree Mlambo and Ippolito, {Matthew M.} and Elizabeth Nenortas and Rannard, {Steve P.} and Andrew Owen and Shapiro, {Theresa A.}",
note = "Funding Information: We thank Charles Flexner for linking this collaboration; David Sullivan for thoughtful discussions; Emily Caton and Mary Barry for laboratory support; Teri Parsons and Mark Marzinke for assistance with atovaquone assays; and Professor Gary Posner for generously gifting LC-MS instrumentation. We are grateful to the Insect and Parasite Core Facilities of the Johns Hopkins Malaria Research Institute for mosquito rearing and provision of sporozoites. This work was supported by a Johns Hopkins Malaria Research Institute Pilot grant and by the Bloomberg Philanthropies (to T.A.S.), by R01AI095453 (to T.A.S.) for atovaquone assay development, and by fellowship support from the National Institutes of Health (T32GM066691) and the Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases (to M.M.I.). Infrastructure and methods employed in this work were developed with support from the Engineering and Physical Science Research Council (EP/G066272/1, EP/K002201/1, EP/L02635X/1) and the National Institutes of Health (R24AI118397, R01AI114405-01) (to A.O. and S.P.R.). Publisher Copyright: {\textcopyright} 2018 The Author(s). Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-017-02603-z",
language = "English (US)",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}