Antioxidant response and biocompatibility of curcumin-loaded triblock copolymeric micelles.

To evaluate the safety profile of cationic micelles, based on triblock copolymer poly(dimethylaminoethyl methacrylate)-poly(e-caprolactone)-poly(dimethylaminoethyl methacrylate) (PDMAEMA9- PCL70-PDMAEMA9), the effects of empty (PM) and curcumin loaded micelles (PM-Curc) on nonenzyme induced lipid peroxidation (LPO) in vitro, hemolytic activity and morphological changes in some organs after repeated intraperitoneal administration in vivo were studied. To induce LPO, rat liver microsomes were incubated with a solution of iron sulfate and ascorbinic acid (Fe2+/AA). The effect of empty PM (40 and 100 µg/ml), PM-Curc and free curcumin (both at 3.48 and 8.7 µg curcumin/ml) was assessed at 20 min incubation time. In the non-enzyme induced LPO model, the investigated substances at all concentrations significantly decreased the formation of malondialdehyde (MDA), compared to the Fe2+/AA induced LPO group. According to the results it can be concluded that curcumin alone and loaded in PM, exert significant antioxidant activity. In the biocompatibility safety studies, the mean hemolytic index for polymeric carrier was less than 2%, indicating it was non-hemolytic. The general appearance of the organ tissues from Wistar rats, treated in vivo with curcumin loaded PM was similar to that of controls, thus showing no apparent toxicity after repeated 14-days treatment.

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

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.