Nanostructured lipid carriers of artemether-lumefantrine combination for intravenous therapy of cerebral malaria.
Patients with cerebral malaria (CM) are unable to take oral medication due to impaired consciousness and vomiting thus necessitating parenteral therapy. Quinine, artemether, and artesunate which are currently used for parenteral malaria therapy have their own drawbacks. The World Health Organization (WHO) has now banned monotherapy and recommends artemisinin-based combination therapy for malaria treatment. However, presently there is no intravenous formulation available for combination therapy of malaria. Artemether-Lumefantrine (ARM-LFN) is a WHO approved combination for oral malaria therapy. However, the low aqueous solubility of ARM and LFN hinders their intravenous delivery. The objective of this study was to formulate ARM-LFN nanostructured lipid carriers (NLC) for intravenous therapy of CM. ARM-LFN NLC were prepared by microemulsion template technique and characterized for size, drug content, entrapment efficiency, drug release, crystallinity, morphology, amenability to autoclaving, compatibility with infusion fluids, stability, antimalarial efficacy in mice, and toxicity in rats. The ARM-LFN NLC showed sustained drug release, amenability to autoclaving, compatibility with infusion fluids, good stability, complete parasite clearance and reversal of CM symptoms with 100% survival in Plasmodium berghei-infected mice, and safety in rats. The biocompatible ARM-LFN NLC fabricated by an industrially feasible technique offer a promising solution for intravenous therapy of CM.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, Maharashtra, India.
Priyanka
P
Prabhu
Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, Maharashtra, India.
Shital
S
Suryavanshi
Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, Maharashtra, India.
Sulabha
S
Pathak
Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, Maharashtra, India.
Aditya
A
Patra
Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, Maharashtra, India.
Shobhona
S
Sharma
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, Maharashtra, India. Electronic address: vbp_muict@yahoo.co.in.
Vandana
V
Patravale
D061605:Administration, Intravenous; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D004338:Drug Combinations; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions; D004983:Ethanolamines / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D008055:Lipids / Q000737:chemistry; D016779:Malaria, Cerebral / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D010962:Plasmodium berghei / Q000302:isolation & purification; D017208:Rats, Wistar
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004337:Drug Carriers; D004338:Drug Combinations; D004655:Emulsions; D004983:Ethanolamines; D005449:Fluorenes; D008055:Lipids
Artemether; Cerebral malaria; Intravenous; Lumefantrine; Nanostructured lipid carriers; Plasmodium