title: Artemether-lumefantrine nanostructured lipid carriers for oral malaria therapy: Enhanced efficacy at reduced dose and dosing frequency.
abstract: Artemether-lumefantrine (ARM-LFN) is a World Health Organization (WHO) approved fixed-dose combination having low solubility and poor oral bioavailability. Nanostructured lipid carriers (NLC) were developed to enhance the oral efficacy of this combination using the microemulsion template technique. They were characterized for drug content, entrapment efficiency, size distribution, in vitro release, antimalarial efficacy, and toxicity. The NLC showed sustained drug release. The recommended adult therapeutic dose is 80mg ARM and 480mg LFN (4 tablets) twice a day, which amounts to 160mg ARM and 960mg LFN daily. ARM-LFN NLC given once a day at 1/5 of therapeutic dose (16mg ARM and 96mg LFN) showed complete parasite clearance and 100% survival in Plasmodium berghei-infected mice. 33% of the mice treated with marketed tablets twice a day at the therapeutic dose showed late-stage recrudescence. Thus, NLC showed enhanced efficacy at 1/10 of the daily dose of ARM-LFN. The 10-fold reduced daily dose was formulated in two soft gelatin capsules thus reducing the number of units to be taken at a time by the patient. The capsules showed good stability at room temperature for a year. The NLC were found to be safe in rats. The biocompatible NLC developed using an industrially feasible technique offer a promising solution for oral malaria therapy.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, Maharashtra, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Prabhu
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, Maharashtra, India.
authors.forename: Shital
authors.initials: S
authors.lastname: Suryavanshi
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, Maharashtra, India.
authors.forename: Sulabha
authors.initials: S
authors.lastname: Pathak
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, Maharashtra, India.
authors.forename: Shobhona
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, Maharashtra, India. Electronic address: vb.patravale@ictmumbai.edu.in.
authors.forename: Vandana
authors.initials: V
authors.lastname: Patravale
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000378:metabolism; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage* / Q000378:metabolism; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000078102:Lumefantrine; D008288:Malaria / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D049329:Nanostructures / Q000008:administration & dosage*; D010962:Plasmodium berghei / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004337:Drug Carriers; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D008055:Lipids; D000077549:Artemether; D000078102:Lumefantrine
keywords: Artemether; Lumefantrine; Malaria; Nanostructured lipid carrier; Oral; Soft gelatin capsule