title: In vitro and in vivo toxicity evaluation of cationic PDMAEMA-PCL-PDMAEMA micelles as a carrier of curcumin.
abstract: 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.
authors: Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav str., 1000 Sofia, Bulgaria. Electronic address: virginia_tzankova@abv.bg.
authors: Virginia
authors: V
authors: Tzankova
authors: Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav str., 1000 Sofia, Bulgaria.
authors: Cvetelina
authors: C
authors: Gorinova
authors: Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav str., 1000 Sofia, Bulgaria.
authors: Magdalena
authors: M
authors: Kondeva-Burdina
authors: Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav str., 1000 Sofia, Bulgaria.
authors: Rumiana
authors: R
authors: Simeonova
authors: Department of Anatomy, Histology, Pathology and Forensic Medicine, Medical Faculty of the University of Sofia, 1407 Sofia, Bulgaria.
authors: Stanislav
authors: S
authors: Philipov
authors: Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav str., 1000 Sofia, Bulgaria.
authors: Spiro
authors: S
authors: Konstantinov
authors: Institute of Polymers, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
authors: Petar
authors: P
authors: Petrov
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav str., 1000 Sofia, Bulgaria.
authors: Dimitar
authors: D
authors: Galabov
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav str., 1000 Sofia, Bulgaria.
authors: Krassimira
authors: K
authors: Yoncheva
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002208:Caproates / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects*; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008689:Methacrylates / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D002208:Caproates; D004337:Drug Carriers; D008689:Methacrylates; C000612081:PDMAEMA-b-PCL-b-PDMAEMA; D011108:Polymers; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D003474:Curcumin
keywords: Curcumin; Nano toxicity; Polymeric micelles; Primary rat hepatocytes