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