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Expanding the therapeutic spectrum of artemisinin: Activity against infectious diseases beyond malaria and novel pharmaceutical developments
Thomas Efferth1, Marta R Romero2, Anna Rita Bilia3, Ahmed Galal Osman4, Mahmoud ElSohly5, Michael Wink6, Rudolf Bauer7, Ikhlas Khan8, Maria Camilla Bergonzi3, Jose J G. Marin2
1 Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany
2 Experimental Hepatology and Drug Targeting (HEVEFARM), CIBERehd, IBSAL, University of Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain
3 Department of Chemistry “Ugo Schiff”, University of Florence, via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy
4 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA
5 ElSohly Laboratories, Inc., 5 Industrial Park Drive, Oxford, MS 38655, and Department of Pharmaceutics, University of Mississippi, University, MS 38677, USA
6 Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany
7 Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitätsplatz 4, 8010 Graz, Austria
8 National Center for Natural Products Research, School of Pharmacy; Devision of Pharmacognosy, Department of Biomolecular Sciences, University of Mississippi, University, MS 38677, USA
Correspondence Address:
Thomas Efferth
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz
Germany
 Source of Support: None, Conflict of Interest: None  | 18 |
DOI: 10.15806/j.issn.2311-8571.2016.0002
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The interest of Western medicine in Traditional Chinese Medicine (TCM) as a source of drug leads/new drugs to treat diseases without available efficient therapies has been dramatically augmented in the last decades by the extensive work and the outstanding findings achieved within this kind of medicine. The practice of TCM over thousands of years has equipped scientists with substantial experience with hundreds of plants that led to the discovery of artemisinin (qinghaosu), which is extracted from the medicinal plant Artemisia annua L. (qinghao). The unexpected success of artemisinin in combating malaria has drawn strong attention from the scientific community towards TCM. Artemisinin was discovered by Youyou Tu in 1972. Since then, several novel pharmacological activities based on the well-known properties of the sesquiterpene lactone structure with the oxepane ring and an endoperoxide bridge have been unravelled. Beyond malaria, artemisinin and its derivatives (artemisinins) exert profound activities towards other protozoans (Leishmania, Trypanosoma, amoebas, Neospora caninum, and Eimeria tenella), trematodes (Schistosoma, liver flukes), and viruses (human cytomegalovirus, hepatitis B and C viruses). Less clear is the effect against bacteria and fungi. Based on the promising results of artemisinin and the first generation derivatives (artesunate, artemether, arteether), novel drug development strategies have been pursued. These included the synthesis of acetal- and non-acetal-type artemisinin dimeric molecules as well as developing nanotechnological approaches, e.g. artemisinin-based liposomes, niosomes, micelles, solid lipid nanocarriers, nanostructured lipid carriers, nanoparticles, fullerenes and nanotubes. The current review presents an overview on different aspects of artemisinins, including sources, chemistry, biological/pharmacological properties, types of infectious pathogens that are susceptible to artemisinins in vitro and in vivo, in addition to the advancement in their drug delivery systems utilizing pharmaceutical technology. It would be expected that different therapeutic strategies based on the second and third generation artemisinin derivatives and artemisinin-based drug technologies would be available in the near future to treat specific infectious diseases.
Abbreviations: ARM: Artemether; ARM-LNP: Artemether-loaded lipid nanoparticles; ART: Artemisinin; ACT: Artemisinin-based combination therapies; AC-PL: Artemisinin-curcumin-loaded PEGylated liposomes; ADPs: Artemisinin dimer piperazine derivatives; A-CL: Artemisinin-loaded conventional liposomes, artemisinin-curcumin-loaded; AST: Artesunate; BBB: Blood-brain barrier; AC-CL: Conventional liposomes; A-PL: artemisinin-loaded PEGylated liposomes; DHA: Dihydroartemisinin; %EE: Entrapment efficiency; GNO: Ground nut oil; kDNA: Kinetoplast; LNs: Lipid nanospheres; NPs: Liposomal nanoparticles; MRT: Mean residence times; MPEG: Methoxy polyethylene glycol; NP: Nanoparticle; NLC: Nanostructured lipid carrier; NCEs: New chemical entities; PSM: Plant secondary metabolites; SNL: Solid lipid nanovectors; TCM: Traditional Chinese Medicine; TR: Transferrin; TNBC: Triple negative breast cancer; VM: Vasculogenic mimicry Received 12 January 2016; Accept 3 May 2016
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