Preparation of beta-artemether liposomes, their HPLC-UV evaluation and relevance for clearing recrudescent parasitaemia in Plasmodium chabaudi malaria-infected mice.
Egg phosphatidylcholine-cholesterol liposome formulations containing the antimalarial drug beta-artemether have been prepared and analyzed for their encapsulating capacity, chemical stability, leakage, in vitro release and their therapeutic efficiency against Plasmodium chabaudi infection. A HPLC-UV analysis of beta-artemether liposomes without derivatisation was achieved. A good linearity of y=4437.7 x+469.01 (R(2)=0.9999) with a detection limit of 2 microg ml(-1) was reached. Prior to this, liposomal formulations composed of different molar ratios of EPC-CHOL were prepared to select beta-artemether crystal-free liposome preparations. The formulation corresponding to 4:3 and a total concentration of 300 mg lipids ml(-1) buffer (pH 7.2), which could incorporate as much as 1.5 mg beta-artemether was selected for therapy. A trapping efficiency of nearly 100% was reached, the drug being located in the lipid bilayers. A dialysis test demonstrated that the drug could be reversibly released from the liposomes, reaching equilibrium within 24 h. After 3 months storage at 4 degrees C, no leakage of beta-artemether had occurred indicating a high stability of the liposomes. These liposomes were used to treat mice infected with the virulent rodent malaria parasite Plasmodium chabaudi chabaudi, with a 100% cure by clearing the recrudescent parasitaemia.
Chimanuka
B
B
Departement Farmaceutische Wetenschappen, Farmaceutische Technologie & Fysische Farmacie, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
Gabriëls
M
M
Detaevernier
M-R
MR
Plaizier-Vercammen
J A
JA
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000032:analysis* / Q000737:chemistry; D000077549:Artemether; D037621:Artemisinins; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008081:Liposomes; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy*; D016788:Plasmodium chabaudi / Q000187:drug effects*; D055502:Secondary Prevention; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000032:analysis* / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
D000962:Antimalarials; D037621:Artemisinins; D008081:Liposomes; D012717:Sesquiterpenes; D000077549:Artemether