Du Plessis L.H., Helena C., Van Huysteen E., Wiesner L., Kotzé A.F.
Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2531, South Africa; Department of Pharmacology, Medical School, University of Cape Town, Cape Town, South Africa
Du Plessis, L.H., Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2531, South Africa; Helena, C., Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2531, South Africa; Van Huysteen, E., Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2531, South Africa; Wiesner, L., Department of Pharmacology, Medical School, University of Cape Town, Cape Town, South Africa; Kotzé, A.F., Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2531, South Africa
Objectives Mefloquine (MQ) is an antimalarial drug with high efficacy, often used in the treatment and chemoprophylaxis of malaria. However, it has low solubility in water, a long elimination half-life (4 days), and is neurotoxic, which leads to unwanted side effects. Methods We investigated a lipid-based drug delivery system, Pheroid vesicles, in combination with MQ (Pheroid MQ), to promote future clinical use. MQ was incorporated into Pheroid vesicles and the formulations characterized. The formulations were evaluated in terms of in-vitro efficacy and toxicity. In-vivo bioavailability studies were conducted in C57 BL6 mice. Key findings The vesicles incorporated MQ with ∼63% entrapment efficiency. The IC50 values of MQ after 48-h incubation in chloroquine-resistant (RSA11) and chloroquine sensitive (3D7) strains, were reduced by ∼50% and ∼30% respectively. In-vivo bioavailability study revealed no change in the pharmacokinetic parameters of MQ, and the incorporation of the drug in Pheroid vesicles reduced the in-vitro haemolytic activity by ∼75%. Furthermore, the cytotoxicity against human neuroblastoma cells (SH-SY5Y) of the free drug was reduced by ∼64% with Pheroid MQ. Conclusions Pheroid vesicles may therefore decrease the toxicity of MQ and thereby improve its therapeutic index, a strategy that may provide an effective alternative for malaria chemoprophylaxis and treatment. © 2013 Royal Pharmaceutical Society.
chloroquine; drug carrier; mefloquine; pheroid vesicle; unclassified drug; animal experiment; article; controlled study; drug bioavailability; drug blood level; drug cytotoxicity; drug delivery system; drug dosage form comparison; drug efficacy; drug formulation; entrapment efficiency; hemolysis; human; human cell; IC 50; in vitro study; in vivo study; malaria; male; mouse; neuroblastoma cell; nonhuman; pharmacological parameters; Plasmodium falciparum; lipid-based drug delivery system; malaria; mefloquine; Pheroid technology; toxicity; Animals; Biological Availability; Cell Line, Tumor; Chemistry, Pharmaceutical; Chloroquine; Coated Vesicles; Drug Delivery Systems; Half-Life; Humans; Malaria; Male; Mefloquine; Mice; Mice, Inbred C57BL; Neuroblastoma; Particle Size; Solubility