Long-acting injectable atovaquone nanomedicines for malaria prophylaxis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29358624.
- Also identified by DOI 10.1038/s41467-017-02603-z and PMC identifier 5778127.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-1</sup> 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.
Medical subject headings
- Antimalarials
- Atovaquone
- Drug Carriers
- Malaria
- Plasmodium berghei