Curcumin-Artesunate Based Polymeric Nanoparticle; Antiplasmodial and Toxicological Evaluation in Murine Model

Abstract

Mainstay chemotherapy for malaria is often faced with the problem of instability and poor bio-distribution thus resulting in impaired pharmacokinetics. Nanomedicine has been acclaimed for its success in drug delivery and improved efficacy. The aim of the study was to assess the antiplasmodial efficacy and safety of curcumin-artesunate co-entrapped nanoparticle in mice model. Curcumin (C) and artesunate (A) were loaded in poly (d,l-lactic-co-glycolic acid) (PLGA) using solvent evaporation from oil-in-water single emulsion method. The nanoparticle formed was characterized for size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The in vitro release of the drug was also determined. The in vivo antiplasmodial activity of CA-PLGA nanoparticle was tested on Plasmodium berghei at 5 and 10 mg/kg doses. The drug efficacy was determined at day 5 and 8. Hematological and hepatic toxicity assays were performed. The mean particle size of drug entrapped PLGA-nanoformulation was 251.1 ± 12.6 nm. The drug entrapment efficiency was 22.3 ± 0.4%. There was a sustained drug release from PLGA for 7 days. The percentage suppression of P. berghei was consistently significantly higher in CA-PLGA 5 mg/kg at day 5 (79.0%) and day 8 (72.5%) than the corresponding values 65.3 and 64.2% in the positive control group (p < 0.05). Aspartate aminotransferase (AST) was significantly lower in mice exposed to 5 mg/kg (42.0 ± 0.0 U/L) and 10 mg/kg (39.5 ± 3.5 U/L) nanotized CA-PLGA compared with the negative control (45.0 ± 4.0 U/L) (p < 0.05). Although alanine aminotransferase (ALT) was lower in nanotized CA-PLGA, the variation was not significant compared with the negative control (p > 0.05). No significant difference in the mean values of the different blood parameters in all exposed groups with the exception of platelets which were significantly higher in the positive control group. A simple method of dual entrapment of curcumin and artesunate with better antiplasmodial efficacy and low toxicity has been synthesized.

Promising nanomaterials in the fight against malaria

“…97 Biodegradable synthetic polymers such as poly(D,L-lactic-coglycolic acid) (PLGA), polyalkylcyanoacrylates or poly(D,L-lactic acid) have been broadly used to prepare polymeric NPs. 6,98 Some studies with PLGA NPs included the synergistic co-delivery of CQ and the antibiotic azithromycin 99 (the most potent antimalarial macrolide widely studied in combination with other antimalarial drugs to improve their efficacy 100 ) and the co-encapsulation of ATS and curcumin 101 as promising combination therapies for malaria.…”

An ImmunoPEGliposome for Targeted Antimalarial Combination Therapy at the Nanoscale

“…Co-nanoencapsulation of the antimalarials quinine and curcumin in polysorbate-coated polymeric nanoparticles inhibited P. falciparum growth in vitro to a slightly larger extent than identical amounts of the unencapsulated drugs [48]. In an in vivo study with the murine malaria species Plasmodium berghei , curcumin-artesunate co-entrapped in poly(D,L-lactic- co -glycolic acid) nanoparticles resulted in significant parasitemia reduction and increased mice survival when compared with the free compounds [49].…”

Porphyrin Derivative Nanoformulations for Therapy and Antiparasitic Agents

“…More complex nanoformulations can be used to perform combination therapy, whereby two or more therapeutic agents are incorporated in the same particle [186,191,192]. One example for malaria treatment of P. berghei-infected mice was based on the administration of a liposomal formulation loaded with curcuminoids in combination with α/β arteether.…”