In vitro and in vivo toxicity evaluation of cationic PDMAEMA-PCL-PDMAEMA micelles as a carrier of curcumin

•The safety data of free and curcumin loaded cationic micelles is presented.•Cationic micelles show low or absent toxicity in two liver cell systems in vitro.•Lack of toxicity changes, e.g. hematopoietic and liver tissue damages are observed in vivo.

Polymeric micelles have attracted significant attention because of their potential application as promising drug-delivery systems. In the present study cationic micelles, based on triblock copolymer poly(dimethylaminoethyl methacrylate) - poly(e-caprolactone) - poly(dimethylaminoethyl methacrylate) were prepared and loaded with curcumin. In vitro cytotoxicity of empty and curcumin loaded polymer micelles was investigated on two cell culture models, human hepatoma cell line HEP G2 and freshly isolated rat hepatocytes, following their viability and lactate dehydrogenase (LDH) leakage. MTT dye reduction assay and LDH release study showed that empty cationic micelles did not cause significant changes in cell viability and membrane integrity at the concentration range from 10.0 to 80.0 μg/ml. Our special attention was focused on the effects of empty and curcumin loaded micelles on oxidative stress markers malondialdehyde (MDA) and reduced glutathione (GSH). The increase in the micelles concentration to 100 μg/ml was accompanied by GSH depletion and increased levels of MDA production in isolated rat hepatocytes. The in vivo toxicity of polymeric micelles was examined in male Wistar rats. The results showed that neither single (7.5 mg/kg, i.p.), nor repeated (3.5 mg/kg, i.p., 14 days) exposure to empty or curcumin loaded polymeric micelles induced any toxicity changes, e.g. hematopoietic and liver tissue damages.