Formulation and evaluation of Pheroid vesicles containing mefloquine for the treatment of malaria.

Abstract

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.

• Authors: Lissinda H du Plessis, Chrizaan Helena, Este van Huysteen, Lubbe Wiesner, Awie F Kotzé
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 66 Issue 1 Pg. 14-22 (Jan 2014) ISSN: 2042-7158 [Electronic] England
• PMID: 24117456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Royal Pharmaceutical Society.

Chemical References

• Chloroquine
• Mefloquine

Topics

• Animals
• Biological Availability
• Cell Line, Tumor
• Chemistry, Pharmaceutical (methods)
• Chloroquine (pharmacology)
• Coated Vesicles (chemistry)
• Drug Delivery Systems (methods)
• Half-Life
• Humans
• Malaria (drug therapy)
• Male
• Mefloquine (chemistry, pharmacology)
• Mice
• Mice, Inbred C57BL
• Neuroblastoma (drug therapy)
• Particle Size
• Solubility