Heparin-Coated Liposomes Improve Antiplasmodial Activity and Reduce the Toxicity of Poupartone B

Abstract Poupartone B is an alkyl cyclohexenone derivative isolated from Poupartia borbonica . This compound demonstrated promising antimalarial activity (IC 50 < 1 µg/mL), however, it was not devoid of toxicity. Thus, to reduce the adverse side effects of this natural bioactive molecule, a deliv...

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Published in:Planta Medica International Open 2020-05, Vol.7 (2), p.e73-e80
Main Authors: Ledoux, Allison, Mamede, Lucia, Palazzo, Claudio, Furst, Tania, Jansen, Olivia, De Tullio, Pascal, Kagisha, Védaste, Pendeville, Hélène, Fillet, Marianne, Piel, Géraldine, Frédérich, Michel
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Language:English
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Summary:Abstract Poupartone B is an alkyl cyclohexenone derivative isolated from Poupartia borbonica . This compound demonstrated promising antimalarial activity (IC 50 < 1 µg/mL), however, it was not devoid of toxicity. Thus, to reduce the adverse side effects of this natural bioactive molecule, a delivery strategy involving a nanostructure was formulated. Additionally, poupartone B-loaded liposomes were coated with heparin, a glycosaminoglycan that is known to target proteins on the surface of Plasmodium falciparum -infected red blood cells. The quantification of the compound in the formulation was performed by HPLC-DAD, while heparin was quantitated by 1 H NMR spectroscopy. The liposomes’ antiplasmodial activity was tested on artemisinin-resistant P. falciparum isolate, and toxicity was evaluated on human HeLa cells and zebrafish embryos. Throughout this research, the formulation demonstrated higher antiplasmodial activities against both P. falciparum strains and a significant decrease of in vitro toxicity. The formulation improved the selectivity index 2 times in vitro and proved to be 3 times less toxic than the compound alone in the zebrafish embryo acute toxicity test. Hence, the use of this strategy to deliver natural products in Plasmodium -infected cells, particularly those with a narrow therapeutic margin, is proposed.
ISSN:2509-9264
2509-6656
DOI:10.1055/a-1158-0569