Matshe, WilliamMvango, SindisiweMalabi, RudzaniTantoh, AsongweAndraos, CharleneFamuyide, Ibukun MichaelMcGaw, Lyndy JoyBaijnath, SoorajPilcher, Lynne A.Balogun, Mohammed2025-10-172025-10-172025-10Matshe, W., Mvango, S., Malabi, R. et al. 2025, 'Oligochitosan conjugates of the antimalarials dihydroartemisinin and lumefantrine: synthesis, stability, cell viability, and antiplasmodial studies', Applied Research, vol. 4, no. 5, art. e70041, pp. 1-14, doi : 10.1002/appl.70041.2702-4288 (print)2702-4288 (online)10.1002/appl.70041http://hdl.handle.net/2263/104752DATA AVAILABILITY STATEMENT : The data that support the findings of this study are available from the corresponding author upon reasonable request.Malaria is treatable with several combinations of drugs, the most well-known and currently most effective being artemisinin-based therapies. Gastrointestinal absorption of these drugs can be poor and erratic if not taken with a fatty meal. Nausea and the loss of appetite, common symptoms of even mild malaria, can therefore jeopardize the effectiveness of the treatment. To enhance the bioavailability of artemisinin-based combination therapies, several lipid-based formulations and delivery systems have been investigated. In this study, we synthesized oligochitosan conjugates of the antimalarial drugs dihydroartemisinin and lumefantrine and examined their physical stability and biological activities. The hydrodynamic properties of both conjugates varied unpredictably under pH conditions like those found at different stages along the gastrointestinal tract and in plasma. The viability of Caco-2 cells exposed to the conjugates was also investigated in comparison to the free drugs. Both conjugates demonstrated significantly lower cytotoxicity compared to the free drugs at concentrations up to 0.5 mg/mL, particularly during the first 24 h of exposure. Despite this, they retained their antiplasmodial effect against Plasmodium falciparum in an in vitro assay at 1 µg/mL and 5 µg/mL. These new chitosan biomaterials hold great potential for further development into oral therapeutics that would not require fatty meal intake due to the intrinsic mucoadhesiveness of chitosan.en© 2025 The Author(s). Applied Research published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License..AntimalarialsArtemisininsBiopolymersConjugatesDelivery systemsLumefantrineOligochitosanMalariaArticle