Title:Combinatorial Effects of Monensin in Liposome Formulations with Antimalarial Drugs Against Blood Stages of Plasmodium falciparum in Culture and P. berghei Infection
Volume: 13
Issue: 1
Author(s): Vinoth Rajendran*, Manendra Pachauri and Prahlad C. Ghosh*
Affiliation:
- Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi 110021,India
- Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi 110021,India
Keywords:
Drug combinations, liposome monensin, plasmodium, antimalarials, chemotherapy.
Abstract: Background: Monensin is a broad spectrum polyether antibiotic produced by
Streptomyces cinnamonensis. It is widely used as veterinary medicine in the treatment of
coccidiosis.
Objective: The goal of this study was to assess the antimalarial efficacy of monensin in
liposomal form in combination with potent antimalarial drugs like chloroquine,
piperaquine, or FR900098 in free form under in vitro and in vivo condition.
Method: In vitro drug sensitivity assay for different drug combinations against blood
stages of chloroquine susceptible (3D7) and chloroquine resistant (INDO) strains of
Plasmodium falciparum in culture was assessed by [3H]-hypoxanthine incorporation assay.
In vivo efficacy was evaluated using the standard 4-day Peters’ test in established
mice models of both Plasmodium berghei NK65 and lethal strain of P. berghei ANKA.
Results: Our results indicate that monensin exhibits superior efficacy than partner antimalarial
drugs tested. The drug combinations between monensin/chloroquine, monensin/
piperaquine, and monensin/FR900098 showed synergistic to additive action, at their 50-
percent inhibitory concentrations (IC50s) against P. falciparum strains in culture.
Monensin in liposomal formulations in combination with subcurative doses of partner
antimalarial drugs effectively reduced parasitic burden in P. berghei infected mice than
comparable doses of antimalarial drugs used alone.
Conclusion: Our results demonstrate that liposomal monensin in combination with partner
antimalarials (chloroquine, piperaquine or FR900098) showed positive interactions
with enhanced parasite killing on P. falciparum strains and P. berghei infection in murine
model. This approach may provide a promising chemotherapeutic regimen at lower doses
for treating human malarial infections.
