CC BY-NC-ND 4.0 · Planta Medica International Open 2020; 07(02): e73-e80
DOI: 10.1055/a-1158-0569
Original Papers

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

Allison Ledoux
1  Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Liège, Belgium
,
Lucia Mamede
1  Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Liège, Belgium
,
Claudio Palazzo
2  Laboratory of Pharmaceutical Technology and Biopharmacy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Liège, Belgium
,
Tania Furst
2  Laboratory of Pharmaceutical Technology and Biopharmacy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Liège, Belgium
,
Olivia Jansen
1  Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Liège, Belgium
,
Pascal De Tullio
3  Laboratory of Pharmaceutical Chemistry, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Liège, Belgium
,
Védaste Kagisha
1  Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Liège, Belgium
,
Hélène Pendeville
4  Plateforme Zebrafish Facility and Transgenics, GIGA, University of Liège, Liège, Belgium
,
Marianne Fillet
5  Laboratory for the Analysis of Medicines, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Liège, Belgium
,
Géraldine Piel
2  Laboratory of Pharmaceutical Technology and Biopharmacy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Liège, Belgium
,
Michel Frédérich
1  Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Liège, Belgium
› Author Affiliations

Abstract

Poupartone B is an alkyl cyclohexenone derivative isolated from Poupartia borbonica. This compound demonstrated promising antimalarial activity (IC50 < 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 1H 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.



Publication History

Received: 04 November 2019
Received: 01 April 2020

Accepted: 13 April 2020

Publication Date:
18 May 2020 (online)

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