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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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024028998 |
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| author | Pesila Akeyo Odera Geoffrey Otieno Joab Otieno Onyango James Jorum Owuor Florence Anyango Oloo Martin Ongas Jeremiah Gathirwa Bernhards Ogutu |
| author_facet | Pesila Akeyo Odera Geoffrey Otieno Joab Otieno Onyango James Jorum Owuor Florence Anyango Oloo Martin Ongas Jeremiah Gathirwa Bernhards Ogutu |
| author_sort | Pesila Akeyo Odera |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T13:50:46Z |
| format | Article |
| id | doaj.art-bf132b97ecae4391823f45b21ab9471e |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:50:46Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-bf132b97ecae4391823f45b21ab9471e2024-04-04T05:04:17ZengElsevierHeliyon2405-84402024-03-01106e26868NANOPARTICLE-BASED formulation of dihydroartemisinin-lumefantrine duo-drugs: Preclinical Evaluation and enhanced antimalarial efficacy in a mouse modelPesila Akeyo Odera0Geoffrey Otieno1Joab Otieno Onyango2James Jorum Owuor3Florence Anyango Oloo4Martin Ongas5Jeremiah Gathirwa6Bernhards Ogutu7School of Chemistry and Material Science, Technical University of Kenya, Nairobi Kenya; Corresponding author.School of Chemistry and Material Science, Technical University of Kenya, Nairobi KenyaSchool of Chemistry and Material Science, Technical University of Kenya, Nairobi KenyaSchool of Chemistry and Material Science, Technical University of Kenya, Nairobi KenyaSchool of Chemistry and Material Science, Technical University of Kenya, Nairobi Kenya; Centre for Research in Therapeutic Sciences, Strathmore University Medical Centre, Nairobi, KenyaCentre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; Centre for Research in Therapeutic Sciences, Strathmore University Medical Centre, Nairobi, KenyaCentre of Traditional Medicine and Drug Research, Kenya Medical Research Institute, Nairobi, KenyaCentre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; Centre for Research in Therapeutic Sciences, Strathmore University Medical Centre, Nairobi, KenyaArtemisinin-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.http://www.sciencedirect.com/science/article/pii/S2405844024028998NanoformulationMalariaLumefantrinedihydroartemisininAntimalarialsToxicity |
| spellingShingle | Pesila Akeyo Odera Geoffrey Otieno Joab Otieno Onyango James Jorum Owuor Florence Anyango Oloo Martin Ongas Jeremiah Gathirwa Bernhards Ogutu NANOPARTICLE-BASED formulation of dihydroartemisinin-lumefantrine duo-drugs: Preclinical Evaluation and enhanced antimalarial efficacy in a mouse model Heliyon Nanoformulation Malaria Lumefantrine dihydroartemisinin Antimalarials Toxicity |
| title | NANOPARTICLE-BASED formulation of dihydroartemisinin-lumefantrine duo-drugs: Preclinical Evaluation and enhanced antimalarial efficacy in a mouse model |
| title_full | NANOPARTICLE-BASED formulation of dihydroartemisinin-lumefantrine duo-drugs: Preclinical Evaluation and enhanced antimalarial efficacy in a mouse model |
| title_fullStr | NANOPARTICLE-BASED formulation of dihydroartemisinin-lumefantrine duo-drugs: Preclinical Evaluation and enhanced antimalarial efficacy in a mouse model |
| title_full_unstemmed | NANOPARTICLE-BASED formulation of dihydroartemisinin-lumefantrine duo-drugs: Preclinical Evaluation and enhanced antimalarial efficacy in a mouse model |
| title_short | NANOPARTICLE-BASED formulation of dihydroartemisinin-lumefantrine duo-drugs: Preclinical Evaluation and enhanced antimalarial efficacy in a mouse model |
| title_sort | nanoparticle based formulation of dihydroartemisinin lumefantrine duo drugs preclinical evaluation and enhanced antimalarial efficacy in a mouse model |
| topic | Nanoformulation Malaria Lumefantrine dihydroartemisinin Antimalarials Toxicity |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024028998 |
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