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dc.contributor.authorShah, S.M.H.
dc.contributor.authorUllah, F.
dc.contributor.authorKhan, Shahzeb
dc.contributor.authorShah, S.M.M.
dc.contributor.authorde Matas, Marcel
dc.contributor.authorHussain, Z.
dc.contributor.authorMinhas, M.U.
dc.contributor.authorAbdEl-Salam, N.M.
dc.contributor.authorAssi, Khaled H.
dc.contributor.authorIsreb, Mohammad
dc.date.accessioned2016-12-22T11:30:45Z
dc.date.available2016-12-22T11:30:45Z
dc.date.issued2016-11-24
dc.identifier.citationShah SMH, Ullah F, Khan S et al (2016) Smart nanocrystals of artemether: fabrication, characterization, and comparative in vitro and in vivo antimalarial evaluation. Drug Design, Development and Therapy. 10: 3837-3850.en_US
dc.identifier.urihttp://hdl.handle.net/10454/11037
dc.descriptionYesen_US
dc.description.abstractArtemether (ARTM) is a very effective antimalarial drug with poor solubility and consequently low bioavailability. Smart nanocrystals of ARTM with particle size of 161±1.5 nm and polydispersity index of 0.172±0.01 were produced in <1 hour using a wet milling technology, Dena® DM-100. The crystallinity of the processed ARTM was confirmed using differential scanning calorimetry and powder X-ray diffraction. The saturation solubility of the ARTM nanocrystals was substantially increased to 900 µg/mL compared to the raw ARTM in water (145.0±2.3 µg/mL) and stabilizer solution (300.0±2.0 µg/mL). The physical stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C-8°C and 25°C were very stable compared to the samples stored at 40°C. The nanocrystals were also shown to be stable when processed at acidic pH (2.0). The solubility and dissolution rate of ARTM nanocrystals were significantly increased (P<0.05) compared to those of its bulk powder form. The results of in vitro studies showed significant antimalarial effect (P<0.05) against Plasmodium falciparum and Plasmodium vivax. The IC50 (median lethal oral dose) value of ARTM nanocrystals was 28- and 54-fold lower than the IC50 value of unprocessed drug and 13- and 21-fold lower than the IC50 value of the marketed tablets, respectively. In addition, ARTM nanocrystals at the same dose (2 mg/kg) showed significantly (P<0.05) higher reduction in percent parasitemia (89%) against P. vivax compared to the unprocessed (27%), marketed tablets (45%), and microsuspension (60%). The acute toxicity study demonstrated that the LD50 value of ARTM nanocrystals is between 1,500 mg/kg and 2,000 mg/kg when given orally. This study demonstrated that the wet milling technology (Dena® DM-100) can produce smart nanocrystals of ARTM with enhanced antimalarial activities.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://dx.doi.org/10.2147%2FDDDT.S114962en_US
dc.rights(c) 2016 Shah et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.en_US
dc.subjectAntimalarial activity; Artemether; in vitro dissolution; Milling; Nanosuspension; Smart nanocrystalsen_US
dc.titleSmart nanocrystals of artemether: fabrication, characterization, and comparative in vitro and in vivo antimalarial evaluationen_US
dc.status.refereedYesen_US
dc.date.Accepted2016-08-29
dc.typeArticleen_US
dc.type.versionPublished versionen_US
refterms.dateFOA2018-07-25T15:52:55Z


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