title: Development, characterization and antimalarial efficacy of dihydroartemisinin loaded solid lipid nanoparticles.
abstract: Effective use of dihydroartemisinin (DHA) is limited by poor water-solubility, poor pharmacokinetic profile and unsatisfactory clinical outcome especially in monotherapy. To reduce such limitations, we reformulated DHA into solid lipid nanoparticles (SLNs) as a nanomedicine drug delivery system. DHA-SLNs were characterized for physical parameters and evaluated for in vitro and in vivo antimalarial efficacy. DHA-SLNs showed desirable particle characteristics including particle size (240.7 nm), particle surface charge (+17.0 mV), drug loadings (13.9 wt %), encapsulation efficacy (62.3%), polydispersity index (0.16) and a spherical appearance. Storage stability up to 90 days and sustained release of drug over 20 h was achieved. Enhanced in vitro (IC50 0.25 ng/ml) and in vivo (97.24% chemosuppression at 2mg/kg/day) antimalarial activity was observed. Enhancement in efficacy was 24% when compared to free DHA. These encouraging results show potential of using the described formulation for DHA drug delivery for clinical application.
  
  
  BACKGROUND
  Malaria still poses a significant problem worldwide. One of the current drugs, artemisinin has been shown to be effective, but has poor water-solubility. The authors here described their formulation of making dihydroartemisinin (DHA) into solid lipid nanoparticles, with subsequent enhancement in efficacy. These results would have massive potential in the clinical setting.
authors.affiliation: Department of Chemistry, Maasai Mara University, Narok, Kenya; Department of Chemistry, Jaramogi Oginga Odinga University of Science and Technology Bondo, Kenya.
authors.forename: Wesley N
authors.initials: WN
authors.lastname: Omwoyo
authors.affiliation: Department of Polymers and Composites, Council for Scientific and Industrial Research, Pretoria, South Africa.
authors.forename: Paula
authors.initials: P
authors.lastname: Melariri
authors.affiliation: Kenya Medical Research Institute, Nairobi, Kenya; Center for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya. Electronic address: jgathirwa@kemri.org.
authors.forename: Jeremiah W
authors.initials: JW
authors.lastname: Gathirwa
authors.affiliation: Center for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya; Department of Chemical Science and Technology, Technical University of Kenya, Nairobi, Kenya.
authors.forename: Florence
authors.initials: F
authors.lastname: Oloo
authors.affiliation: Department of Chemistry, Jaramogi Oginga Odinga University of Science and Technology Bondo, Kenya.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Mahanga
authors.affiliation: Department of Polymers and Composites, Council for Scientific and Industrial Research, Pretoria, South Africa.
authors.forename: Lonji
authors.initials: L
authors.lastname: Kalombo
authors.affiliation: Kenya Medical Research Institute, Nairobi, Kenya; Center for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya.
authors.forename: Bernhards
authors.initials: B
authors.lastname: Ogutu
authors.affiliation: Department of Polymers and Composites, Council for Scientific and Industrial Research, Pretoria, South Africa.
authors.forename: Hulda
authors.initials: H
authors.lastname: Swai
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D037621:Artemisinins / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008288:Malaria / Q000188:drug therapy*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010961:Plasmodium / Q000187:drug effects*; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004337:Drug Carriers; D008055:Lipids; C039060:artenimol
keywords: Dihydroartemisinin; Nanomedicine drug delivery; Solid lipid nanoparticles