Arteether nanoemulsion for enhanced efficacy against Plasmodium yoelii nigeriensis malaria: an approach by enhanced bioavailability.

Abstract

The present work is focused on the preparation of nanoemulsions (NEs) loaded with arteether (ART) for its enhanced efficacy against malaria parasites. ART-NEs have been prepared using high pressure homogenization (HPH) technique with the aim of improving its solubility and thus its bioavailability. ART-NEs were optimized in terms of pressure and number of cycles. Globule size and size distributions were chosen as quality parameters. The maximum drug loading was achieved up to 93 ± 7.4% with globule size 156 ± 10.2 nm and zeta potential of -23.3 ± 3.4 mV. The developed ART-NEs were found to be stable in terms of globule size and size distribution at different pH. The in vitro release profile of the ART-NEs showed 62% drug release within 12h. The percentage cell viability of blank NEs were within acceptable limits. A sensitive assay method for the determination of ART in rat plasma by liquid chromatography-mass spectrometry (LC-MS) was employed after oral administration of ART-NEs. The pharmacokinetic study showed significantly enhanced bioavailability of ART in ART-NE-V. The area under curve (AUC) of ART-NE-V was AUC0-t 1988.411 ± 119.66 h ng/ml which was significantly higher (p<0.05) than ART in ground nut oil (GNO) AUC0-t 671.852 ± 187.05 h ng/ml. The Cmax of ART-NE-V (1506 ± 161.22 ng/ml) was also significantly higher (p<0.05) than ART in GNO (175.2 ± 16.54 ng/ml) and ART given intramuscularly (IM) (278.05 ± 38.59 ng/ml). The ART-NE-V was having significantly high antimalarial efficacy and survival rate of mice giving 80% cure rate at 12.5 mg/kg for 5 days in comparison to 30% cure rate of ART in GNO at the same daily dose and it was also comparable to the 100% cure rate at 12.5 mg/kg for 5 days for ART given intramuscularly. In conclusion ART-NE can be a promising oral delivery system for ART.

• Authors: Pankaj Dwivedi, Renuka Khatik, Priyanka Chaturvedi, Kiran Khandelwal, Isha Taneja, Kanumuri Siva Rama Raju, Hemlata Dwivedi, Sunil Kumar Singh, Pramod Kumar Gupta, Prashant Shukla, Priyanka Tripathi, Sarika Singh, Renu Tripathi, Wahajuddin, Sarvesh Kumar Paliwal, Anil Kumar Dwivedi, Prabhat Ranjan Mishra
• Journal: Colloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 126 Pg. 467-75 (Feb 01 2015) ISSN: 1873-4367 [Electronic] Netherlands
• PMID: 25616971 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antimalarials
• Artemisinins
• Emulsions
• artemotil

Topics

• Administration, Oral
• Animals
• Antimalarials (administration & dosage, blood, pharmacokinetics, pharmacology)
• Artemisinins (administration & dosage, blood, pharmacokinetics, pharmacology)
• Biological Availability
• Caco-2 Cells
• Cell Line
• Cell Survival (drug effects)
• Emulsions (chemistry)
• Humans
• Malaria (drug therapy, parasitology)
• Mice
• Nanostructures (chemistry)
• Parasitic Sensitivity Tests
• Particle Size
• Plasmodium yoelii (drug effects)
• Rats
• Surface Properties