title: Formulation and evaluation of Pheroid vesicles containing mefloquine for the treatment of malaria.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.
authors.forename: Lissinda H
authors.initials: LH
authors.lastname: du Plessis
authors.forename: Chrizaan
authors.initials: C
authors.lastname: Helena
authors.forename: Este
authors.initials: E
authors.lastname: van Huysteen
authors.forename: Lubbe
authors.initials: L
authors.lastname: Wiesner
authors.forename: Awie F
authors.initials: AF
authors.lastname: Kotzé
mesh_terms: D000818:Animals; D001682:Biological Availability; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002738:Chloroquine / Q000494:pharmacology; D018699:Coated Vesicles / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D006207:Half-Life; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009447:Neuroblastoma / Q000188:drug therapy; D010316:Particle Size; D012995:Solubility
chemical_list: D002738:Chloroquine; D015767:Mefloquine
keywords: Pheroid technology; lipid-based drug delivery system; malaria; mefloquine; toxicity