Bakshi RP, Tatham LM, Savage AC, Tripathi AK, Mlambo G, Ippolito MM, Nenortas E, Rannard SP, Owen A, Shapiro TA. Long-acting injectable atovaquone nanomedicines for malaria prophylaxis. Nat Commun. 2018 Jan 22;9(1):315. doi: 10.1038/s41467-017-02603-z. PMID: 29358624; PMCID: PMC5778127.
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.