title: Cationic triblock copolymer micelles enhance antioxidant activity, intracellular uptake and cytotoxicity of curcumin.
abstract: The aim of the present study was to develop curcumin loaded cationic polymeric micelles and to evaluate their loading, preservation of curcumin antioxidant activity and intracellular uptake ability. The micelles were prepared from a triblock copolymer consisting of poly(ϵ-caprolactone) and very short poly(2-(dimethylamino) ethyl methacrylate) segments (PDMAEMA9-PCL70-PDMAEMA9). The micelles showed monomodal size distribution, mean diameter of 145 nm, positive charge (+72 mV), critical micellar concentration around 0.05 g/l and encapsulation efficiency of 87%. The ability of the micellar curcumin to scavenge the ABTS radical and hypochlorite ions was higher than that of the free curcumin. Confocal microscopy revealed that the uptake of curcumin by chronic myeloid leukemia derived K-562 cells and human multiple myeloma cells U-266 was more intensive when curcumin was loaded into the micelles. These results correlated with the higher cytotoxicity of the micellar curcumin compared to free curcumin. Intraperitoneal treatment of Wistar rats indicated that PDMAEMA-PCL-PDMAEMA copolymer, comprising very short cationic chains, did not change the levels of malondialdehyde and glutathione in livers indicating an absence of oxidative stress. Thus, PDMAEMA-PCL-PDMAEMA triblock micelles could be considered efficient and safe platform for curcumin delivery.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria. Electronic address: krassi.yoncheva@gmail.com.
authors.forename: Krassimira
authors.initials: K
authors.lastname: Yoncheva
authors.affiliation: Institute of Polymers, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
authors.forename: Katya
authors.initials: K
authors.lastname: Kamenova
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
authors.forename: Teodora
authors.initials: T
authors.lastname: Perperieva
authors.affiliation: Department of Physics and Biophysics, Medical Faculty, Medical University of Sofia, 1431 Sofia, Bulgaria.
authors.forename: Vera
authors.initials: V
authors.lastname: Hadjimitova
authors.affiliation: Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
authors.forename: Petar
authors.initials: P
authors.lastname: Donchev
authors.affiliation: Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
authors.forename: Kaloyan
authors.initials: K
authors.lastname: Kaloyanov
authors.affiliation: Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
authors.forename: Spiro
authors.initials: S
authors.lastname: Konstantinov
authors.affiliation: Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kondeva-Burdina
authors.affiliation: Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
authors.forename: Virginia
authors.initials: V
authors.lastname: Tzankova
authors.affiliation: Institute of Polymers, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria. Electronic address: ppetrov@polymer.bas.bg.
authors.forename: Petar
authors.initials: P
authors.lastname: Petrov
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D002412:Cations / Q000737:chemistry*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000737:chemistry* / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D020014:K562 Cells; D008297:Male; D008689:Methacrylates / Q000737:chemistry; D008823:Micelles; D009757:Nylons / Q000737:chemistry; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D002412:Cations; D004337:Drug Carriers; D008689:Methacrylates; D008823:Micelles; D009757:Nylons; D011091:Polyesters; D011108:Polymers; C407037:poly(2-(dimethylamino)ethyl methacrylate); C016240:polycaprolactone; D011092:Polyethylene Glycols; D003474:Curcumin
keywords: Antioxidant activity; Cationic polymeric micelles; Curcumin; Intracellular uptake; Oxidative stress