title: Enhanced antimalarial activity by a novel artemether-lumefantrine lipid emulsion for parenteral administration.
abstract: Artemether and lumefantrine (also known as benflumetol) are difficult to formulate for parenteral administration because of their low aqueous solubility. Cremophor EL as an emulsion excipient has been shown to cause serious side effects. This study reports a method of preparation and the therapeutic efficacies of novel lipid emulsion (LE) delivery systems with artemether, lumefantrine, or artemether in combination with lumefantrine, for parenteral administration. Their physical and chemical stabilities were also evaluated. Furthermore, the in vivo antimalarial activities of the lipid emulsions developed were tested in Plasmodium berghei-infected mice. Artemether, lumefantrine, or artemether in combination with lumefantrine was encapsulated in an oil phase, and the in vivo performance was assessed by comparison with artesunate for injection. It was found that the lumefantrine lipid emulsion (LUM-LE) and artemether-lumefantrine lipid emulsion (ARM-LUM-LE-3) (1:6) began to decrease the parasitemia levels after only 3 days, and the parasitemia inhibition was 90% at doses of 0.32 and 0.27 mg/kg, respectively, with immediate antimalarial effects greater than those of the positive-control group and constant antimalarial effects over 30 days. LUM-LE and ARM-LUM-LE-3 demonstrated the best performance in terms of chemical and physical stabilities and antiplasmodial efficacy, with a mean particle size of 150 nm, and they have many favorable properties for parenteral administration, such as biocompatibility, physical stability, and ease of preparation.
authors: School of Medicine, Xi'an Jiaotong University, Xi'an, People's Republic of China Xi'an Libang Pharmaceutical Co., Ltd., Xi'an, People's Republic of China.
authors: Yufan
authors: Y
authors: Ma
authors: Key Laboratory for Space Bioscience and Biotechnology, Faculty of Life, Northwestern Polytechnical University, Xi'an, People's Republic of China.
authors: Tingli
authors: T
authors: Lu
authors: Key Laboratory for Space Bioscience and Biotechnology, Faculty of Life, Northwestern Polytechnical University, Xi'an, People's Republic of China.
authors: Wen
authors: W
authors: Zhao
authors: Key Laboratory for Space Bioscience and Biotechnology, Faculty of Life, Northwestern Polytechnical University, Xi'an, People's Republic of China.
authors: Ying
authors: Y
authors: Wang
authors: Key Laboratory for Space Bioscience and Biotechnology, Faculty of Life, Northwestern Polytechnical University, Xi'an, People's Republic of China.
authors: Ting
authors: T
authors: Chen
authors: Key Laboratory for Space Bioscience and Biotechnology, Faculty of Life, Northwestern Polytechnical University, Xi'an, People's Republic of China.
authors: Qibing
authors: Q
authors: Mei
authors: Key Laboratory for Space Bioscience and Biotechnology, Faculty of Life, Northwestern Polytechnical University, Xi'an, People's Republic of China Shaanxi Liposome Research Center, Xi'an, People's Republic of China Xi'an Libang Pharmaceutical Co., Ltd., Xi'an, People's Republic of China taochen@libang.com.cn.
authors: Tao
authors: T
authors: Chen
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D004655:Emulsions / Q000737:chemistry*; D004983:Ethanolamines / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D000078102:Lumefantrine; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D051379:Mice; D010962:Plasmodium berghei / Q000472:pathogenicity*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004655:Emulsions; D004983:Ethanolamines; D005449:Fluorenes; D000077549:Artemether; D000078102:Lumefantrine