Development and in vitro/in vivo evaluation of artemether and lumefantrine co-loaded nanoliposomes for parenteral delivery |
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Authors: | Kashif Shakeel Sheikh Raisuddin Sadath Ali Syed Sarim Imam Md Akhlaquer Rahman Gaurav Kumar Jain |
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Institution: | 1. Department of Pharmaceutics, Jamia Hamdard, New Delhi, India;2. Faculty of Interdisciplinary Sciences and Technology, Jamia Hamdard, New Delhi, India;3. Azad Institute of Pharmacy and Research, Lucknow, India;4. Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi, India;5. Azad Institute of Pharmacy and Research, Lucknow, India;6. Glocal School of Pharmacy, Glocal University, Saharanpur, India;7. Faculty of Pharmacy, Integral University, Lucknow, India |
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Abstract: | Combination therapy of artemether (ART) and lumefantrine (LUM) is well-established for the treatment of uncomplicated malaria worldwide. Nanoliposomes (NLs) encapsulating both drugs were prepared and freeze-dried. The lyophilized nanoliposomes exhibited high entrapment efficiency of artemether (66.18%), relatively low entrapment efficiency of lumefantrine (53.46%), low average size diameter (125.3?nm) and found to be stable at 4?°C for 60 days without significant change in mean particle diameter and drug entrapment efficiencies. In vitro drug release study has shown initial burst effect and then sustained release pattern over a time period of 30?h. In vivo toxicity study was examined by liver and kidney function test as well as histopathological examination. Nanoliposomes showed lower hemolytic potential (~10%) compared to all the components when studied individually. There was no significant change (p?>?0.05) in biochemical parametes between control and treated group of animals. Pharmacokinetic data of ART?+?LUM NLs showed higher the area under the plasma concentration–time curve (AUC) values and prolonged residence time of drug in the blood circulation compared with ART?+?LUM solution. The tissue distribution demonstrated high uptake of ART?+?LUM-NLs in RES organs particularly in liver and spleen. Biocompatibility was confirmed by hepato- and nephrotoxicity analysis showed no sign of fibrosis, fatty infiltration, centrilobular necrosis and lymphocyte infiltration confirmed the suitability of developed formulation for treatment of malaria. |
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Keywords: | Malaria artemisinin combination therapy nanoliposomes hemolysis histopathology biodistribution |
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