A water-soluble polymer-lumefantrine conjugate for the intravenous treatment of severe malaria

Loading...
Thumbnail Image

Authors

Matshe, William M.R.
Tshweu, Lesego L.
Mvango, Sindisiwe
Cele, Zamani E.D.
Chetty, Avashnee S.
Pilcher, Lynne A.
Famuyide, Ibukun Michael
McGaw, Lyndy Joy
Taylor, Dale
Gibhard, Liezl

Journal Title

Journal ISSN

Volume Title

Publisher

Wiley

Abstract

Uncomplicated malaria is effectively treated with oral artemisinin-based combination therapy (ACT). Yet, there is an unmet clinical need for the intravenous treatment of the more fatal severe malaria. There is no combination intravenous therapy for uncomplicated due to the nonavailability of a water-soluble partner drug for the artemisinin, artesunate. The currently available treatment is a two-part regimen split into an intravenous artesunate followed by the conventional oral ACT . In a novel application of polymer therapeutics, the aqueous insoluble antimalarial lumefantrine is conjugated to a carrier polymer to create a new water-soluble chemical entity suitable for intravenous administration in a clinically relevant formulation . The conjugate is characterized by spectroscopic and analytical techniques, and the aqueous solubility of lumefantrine is determined to have increased by three orders of magnitude. Pharmacokinetic studies in mice indicate that there is a significant plasma release of lumefantrine and production its metabolite desbutyl-lumefantrine (area under the curve of metabolite is ≈10% that of the parent). In a Plasmodium falciparum malaria mouse model, parasitemia clearance is 50% higher than that of reference unconjugated lumefantrine. The polymer-lumefantrine shows potential for entering the clinic to meet the need for a one-course combination treatment for severe malaria.

Description

DATA AVAILABILITY STATEMENT : The data that support the findings of this study are available from the corresponding author upon reasonable request.

Keywords

Drug delivery, Infectious disease, Lumefantrine, Nanomedicine, Polymer therapeutics, Severe malaria, Artemisinin-based combination therapy (ACT), Malaria, SDG-03: Good health and well-being

Sustainable Development Goals

SDG-03:Good heatlh and well-being

Citation

Matshe, W.M.R., Tshweu, L.L., Mvango, S. et al. 2023, 'A water-soluble polymer-lumefantrine conjugate for the intravenous treatment of severe malaria', Macromolecular Bioscience, vol. 23, art. 2200518, pp. 1-12. DOI: 10.1002/mabi.202200518.