Last Updated: 22/07/2025
Atovaquone incorporated into transferrin-modified nanoemulsions: correlation between antimalarial activity and carrier supramolecular structure
Objectives
Considering that the parasite that causes malaria can only capture iron associated with transferrin, its plasma carrier protein, whose receptor is on the membrane of infected erythrocytes, the present proposal aims at the development of transferrin-modified nanoemulsions as carriers of atovaquone, correlating its supramolecular structure to antimalarial effects on P. falciparum culture.
Malaria is a disease caused by protozoa of the genus Plasmodium, which develop inside red blood cells and/or human hepatocytes. Infections with P. falciparum are the most serious and can lead to death of children and adults. Despite a promising trend in reducing the number of disease-related deaths, the numbers are still worrying, prompting the World Health Organization to launch the World Technical Strategy for Malaria 2016-2030, which has, among many goals, development More effective and safe drugs against the disease. Currently, the literature reports resistance or tolerance to all drugs used to treat malaria, including artemisinin derivatives, which until then had been the last effective alternative. Recently, lipid-based nanoemulsions were developed to deliver atovaquone parenterally, achieving 80% inhibition of atovaquone-resistant P. falciparum growth in vitro (data not yet published). Despite the promising results, it is necessary to improve the nanocarrier to achieve complete remission of the infection. Certain molecules have been used to more efficiently transport drugs or nanoparticles into the target cells. The formulations will be delineated through a factorial study 23 in order to investigate the effect of the qualitative and quantitative composition of cationic lipid (DOTAP), hydrophilic polymer (Tween 80) and transferrin binder on the physicochemical properties of nanoemulsions. The antimalarial drug will be incorporated into the optimized formulation. Four control nanoemulsions will also be prepared in order to verify the effect of the presence of atovaquone, DOTAP, Tween 80 and tranferrin on the physico-chemical characteristics and stability of the formulation, on the release of the drug in vitro, on surface morphology (MET and AFM), In the supramolecular organization (SAXS) and in the biological effect of nanostructures on P. falciparum cultures. Thus, a better understanding of the essential requirements for the effectiveness of nanoemulsion carriers for the delivery of drugs for the treatment of malaria is desired, in order to create a platform for the development of this type of release system.
Jun 2017 — May 2020
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