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 (1).
315-.
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: | 19 Jan 2023 06:42 |
| 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 |
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