Antiplasmodial Activity and Toxicological Assessment of Curcumin PLGA-Encapsulated Nanoparticles

Abstract

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.

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

“…Curcumin-artesunate PLGA entrapped nanoparticle (CA-PLGA) was formulated by solvent evaporation from oil-in-water single emulsion method as described by Busari et al ( 2017 ). Briefly, 5 mg each of curcumin and artesunate was added to an organic phase containing homogenous solution of 50 mg PLGA in 3.5 mL of dichloromethane and 0.5 mL of acetone to constitute 1:5 (drugs to PLGA) ratios.…”

“…CA-PLGA nanoparticle diameter, zeta potential and polydispersity index (PDI) were measured by dynamic light scattering (DLS) method using Zetasizer Nano-ZS (Malvern Instruments, UK) as previously described (Busari et al, 2017 ; Dauda et al, 2017 ). The size and PDI of CA-PLGA nanoformulation were determined from nanoparticle suspension of appropriate amount of the drug loaded nanoparticles dispersed in MQ water in a clear disposable sizing cuvette.…”

“…Delivery systems such as poly ( d,l -lactic- co -glycolic acid) (PLGA) have been widely exploited in drug delivery to target intracellular pathogens like malaria parasites (Nayaka et al, 2010 ; Busari et al, 2017 ; Dauda et al, 2017 ). Besides, PLGA was successfully used to deliver antihelminthic and anticancer drugs (Nguyen et al, 2015 ; Oyeyemi et al, 2018 ).…”

Sustained curcumin release from PLGA microspheres improves bone formation under diabetic conditions by inhibiting the reactive oxygen species production

“…Among these drug carriers, poly-lactic-co-glycolic acid (PLGA) microspheres become a preferred choice for its favorable stability, low toxicity, and high encapsulation efficiency for hydrophobic agents. 16 …”

The Impact of Curcumin on Bone Osteogenic Promotion of MC3T3 Cells under High Glucose Conditions and Enhanced Bone Formation in Diabetic Mice

“…Curcumin (CURC), derived from the plant Curcuma longa, is a bioactive component of turmeric with the ability to modulate the immune system [13]. Although curcumin has poor water solubility and low bioavailability and stability, some studies have confirmed that drug carriers such as proteins, polymeric particles, and polylactic-glycolic acid copolymer (PLGA) microspheres can effectively solve this problem and give full play to its antioxidant, anti-inflammatory, and anti-hyperglycemic properties [14][15][16][17][18]. Natural or chemically modified curcumin could upregulate insulin sensitivity and reduce glucose and glycosylated hemoglobin levels, which has great potential as an alternative therapeutic option for diabetes mellitus and its complications [19,20].…”