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.
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 humanneuroblastoma 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: Sindisiwe Mvango; William M R Matshe; Abideen O Balogun; Lynne A Pilcher; Mohammed O Balogun Journal: Pharm Res Date: 2018-10-15 Impact factor: 4.200
Authors: Lizette Grobler; Marina Chavchich; Richard K Haynes; Michael D Edstein; Anne F Grobler Journal: Antimicrob Agents Chemother Date: 2014-10-06 Impact factor: 5.191
Authors: Dário Silva; Márcio V C Lopes; Željko Petrovski; Miguel M Santos; Jussevania P Santos; Sueli F Yamada-Ogatta; Marcelle L F Bispo; Marcus V N de Souza; Ana Rita C Duarte; Maria C S Lourenço; Raoni Schroeder B Gonçalves; Luis C Branco Journal: Molecules Date: 2022-08-13 Impact factor: 4.927