NANOPARTICLE-BASED formulation of dihydroartemisinin-lumefantrine duo-drugs: Preclinical Evaluation and enhanced antimalarial efficacy in a mouse model

Artemisinin-based combinations (ACTs) are World Health Organization-recommended treatment for malaria. Artemether (A) and lumefantrine (LUM) were the first co-formulated ACT and first-line treatment for malaria globally, artemether is dihydroartemisinin's (DHA's) prodrug. Artemisinins and...

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Bibliographic Details
Main Authors: Pesila Akeyo Odera, Geoffrey Otieno, Joab Otieno Onyango, James Jorum Owuor, Florence Anyango Oloo, Martin Ongas, Jeremiah Gathirwa, Bernhards Ogutu
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024028998
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Summary:Artemisinin-based combinations (ACTs) are World Health Organization-recommended treatment for malaria. Artemether (A) and lumefantrine (LUM) were the first co-formulated ACT and first-line treatment for malaria globally, artemether is dihydroartemisinin's (DHA's) prodrug. Artemisinins and LUM face low aqueous solubility while artemisinin has low bioavailability and short half-life thus requiring continuous dosage to maintain adequate therapeutic drug-plasma concentration. This study aimed at improving ACTs limitations by nano-formulating DHA-LUM using solid lipid nanoparticles (SLNs) as nanocarrier. SLNs were prepared by modified solvent extraction method based on water-in-oil-in-water double emulsion. Mean particle size, polydispersity index and zeta potential were 308.4 nm, 0.29 and −16.0 mV respectively. Nanoencapsulation efficiencies and drug loading of DHA and LUM were 93.9%, 33.7%, 11.9%, and 24.10% respectively. Nanoparticles were spherically shaped and drugs followed Kors-Peppas release model, steadily released for over 72 h. DHA-LUM-SLNs were 31% more efficacious than conventional oral doses in clearing Plasmodium berghei from infected Swiss albino mice.
ISSN:2405-8440