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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\u2010soluble partner drug for the artemisinin, artesunate. The currently available treatment is a two\u2010part 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\u2010soluble 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\u2010lumefantrine (area under the curve of metabolite is \u224810% that of the parent). In a <jats:italic>Plasmodium falciparum<\/jats:italic> malaria mouse model, parasitemia clearance is 50% higher than that of reference unconjugated lumefantrine. The polymer\u2010lumefantrine shows potential for entering the clinic to meet the need for a one\u2010course combination treatment for severe malaria.<\/jats:p>","DOI":"10.1002\/mabi.202200518","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T08:48:05Z","timestamp":1680252485000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Water\u2010Soluble Polymer\u2010Lumefantrine Conjugate for the Intravenous Treatment of Severe Malaria"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3040-8413","authenticated-orcid":false,"given":"William M.R.","family":"Matshe","sequence":"first","affiliation":[{"name":"Bio\u2010Polymer Modification and Therapeutics Laboratory Centre for Nanostructures and Advanced Materials CSIR  Pretoria 0001 South 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