title: 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.affiliation: Pharmaceutics Division, Central Drug Research Institute, Lucknow 226031, India; Banasthali Vidyapeeth, Banasthali, Rajasthan 304022, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Dwivedi
authors.affiliation: Pharmaceutics Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Renuka
authors.initials: R
authors.lastname: Khatik
authors.affiliation: Pharmaceutics Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Chaturvedi
authors.affiliation: Pharmaceutics Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Khandelwal
authors.affiliation: Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Isha
authors.initials: I
authors.lastname: Taneja
authors.affiliation: Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Kanumuri Siva Rama
authors.initials: KS
authors.lastname: Raju
authors.affiliation: Parasitology Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Hemlata
authors.initials: H
authors.lastname: Dwivedi
authors.affiliation: Parasitology Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Pharmaceutics Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Gupta
authors.affiliation: Pharmaceutics Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Shukla
authors.affiliation: Pharmaceutics Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Tripathi
authors.affiliation: Toxicology Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Sarika
authors.initials: S
authors.lastname: Singh
authors.affiliation: Parasitology Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Renu
authors.initials: R
authors.lastname: Tripathi
authors.affiliation: Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow 226031, India.
authors.lastname: Wahajuddin
authors.affiliation: Banasthali Vidyapeeth, Banasthali, Rajasthan 304022, India.
authors.forename: Sarvesh Kumar
authors.initials: SK
authors.lastname: Paliwal
authors.affiliation: Pharmaceutics Division, Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Dwivedi
authors.affiliation: Pharmaceutics Division, Central Drug Research Institute, Lucknow 226031, India. Electronic address: mishrapr@hotmail.com.
authors.forename: Prabhat Ranjan
authors.initials: PR
authors.lastname: Mishra
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D037621:Artemisinins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D018938:Caco-2 Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004655:Emulsions / Q000737:chemistry; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology*; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D021261:Parasitic Sensitivity Tests; D010316:Particle Size; D010967:Plasmodium yoelii / Q000187:drug effects*; D051381:Rats; D013499:Surface Properties
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004655:Emulsions; C055141:artemotil
keywords: Antimalarial efficacy; Arteether; High pressure homogenizer; LC–MS; Nanoemulsion; Pharmacokinetics