Long-acting injectable atovaquone nanomedicines for malaria prophylaxis.
Nat Commun
; 9(1): 315, 2018 01 22.
Article
em En
| MEDLINE
| ID: mdl-29358624
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plasmodium berghei
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Portadores de Fármacos
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Atovaquona
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Malária
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Antimaláricos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article