Curcumin has many pharmacological activities despite its poor bioavailability and in vivo stability. Here, we show that a nanoformulated curcumin (PLGA-curcumin) has better therapeutic index than native curcumin in preventing the onset of neurological symptoms and delaying the death of mice in experimental cerebral malaria. Oral PLGA-curcumin was at least as effective as native curcumin at a 15-fold lower concentration in preventing the breakdown of blood-brain barrier and inhibition of brain mRNAs for inflammatory cytokines, chemokine receptor CXCR3 and its ligand CXCL10, with an increase in the anti-inflammatory cytokine IL-10. This was also reflected in serum cytokine and chemokine levels. At equivalent concentrations, a single oral dose of PLGA-curcumin was more effective in inhibiting serum IFNγ levels and enhancing IL-10 levels than native curcumin. Even at low concentrations, PLGA-curcumin was superior to native curcumin in inhibiting the sequestration of parasitized-RBCs and CD8+ T cells in the brain. A single oral dose of 5 mg PLGA-curcumin containing 350 μg of curcumin resulted in 3–4 fold higher concentration and prolonged presence of curcumin in the brain than that obtained with 5 mg of native curcumin, indicating better bioavailability of PLGA-curcumin. PLGA-curcumin has potential as an adjunct drug to treat human cerebral malaria.

Curcumin is a polyphenolic pigment isolated from the rhizomes of Curcuma longa (turmeric), a medicinal plant widely used in the ancient Indian and Chinese medicine. The antiplasmodial activity of curcumin is often hampered by its fast metabolism and poor water solubility, thus its incorporation into a delivery system could circumvent this problem. This study aimed to evaluate the in vivo antiplasmodial activity and the toxicity assessment of curcumin incorporated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Curcumin was loaded with poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation from oil-in-water single emulsion method. The nanoparticles were characterized and evaluated in vivo for antimalarial activities using Peter’s 4-day suppressive protocol in mice model. Hematological and hepatic toxicity assays were performed on whole blood and plasma, respectively. In vivo anti-parasitic test and toxicity assays for free and encapsulated drug were performed at 5 and 10 mg/kg. In vitro cytotoxicity of free and PLGA encapsulated curcumin (Cur-PLGA) to RAW 264.7 cell line was also determined at varying concentrations (1000–7.8 μg/mL). The size and entrapment efficiency of the nanoparticulate drug formulated was 291.2 ± 82.1 nm and 21.8 ± 0.4 respectively. The percentage parasite suppression (56.8%) at 5 mg/kg was significantly higher than in free drug (40.5%) of similar concentration (p < 0.05) but not at 10 mg/kg (49.5%) at 4-day post-treatment. There were no significant differences in most of the recorded blood parameters in free curcumin and PLGA encapsulated nanoparticulate form (p > 0.05) except in lymphocytes which were significantly higher in Cur-PLGA compared to the free drug (p < 0.05). There were no significant differences in hepatotoxic biomarkers; aspartate aminotransferase and alanine aminotransferase concentrations in various treatment groups (p > 0.05). At higher concentrations (1000 and 500 μg/mL), Cur-PLGA entrapped nanoparticle showed higher toxicity compared with the free drug (p < 0.05) in exposed RAW 264.7 cell line. The cell viability was, however, higher in Cur-PLGA nanoparticles than in free curcumin at lower concentrations (p > 0.05). The antiplasmodial activity and safety of Cur-PLGA was better at lower concentration.

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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.

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