title: Curcumin delivery from poly(acrylic acid-co-methyl methacrylate) hollow microparticles prevents dopamine-induced toxicity in rat brain synaptosomes.
abstract: The potential of poly(methyl methacrylate-co-acrylic acid) (PMMA-AA) copolymers to form hollow particles and their further formulation as curcumin delivery system have been explored. The particles were functionalized by crosslinking the acrylic acid groups via bis-amide formation with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazide (DTP) which simultaneously incorporated reversibility due to the presence of disulfide bonds within the crosslinker. Optical micrographs showed the formation of spherical hollow microparticles with a size ranging from 1 to 7 μm. Curcumin was loaded by incubation of its ethanol solution with aqueous dispersions of the cross-linked particles and subsequent evaporation of the ethanol. Higher loading was observed in the microparticles with higher content of hydrophobic PMMA units indicating its influence upon the loading of hydrophobic molecules such as curcumin. The in vitro release studies in a phosphate buffer showed no initial burst effect and sustained release of curcumin that correlated with the swelling of the particles under these conditions. The capacity of encapsulated and free curcumin to protect rat brain synaptosomes against dopamine-induced neurotoxicity was examined. The encapsulated curcumin showed greater protective effects in rat brain synaptosomes as measured by synaptosomal viability and increased intracellular levels of glutathione.
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: 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, Acad. G. Bonchev, Block 103 A, 1113 Sofia, Bulgaria.
authors.forename: Petar
authors.initials: P
authors.lastname: Petrov
authors.affiliation: ICAM Toulouse, 75 Avenue de Grande Bretagne, CS 97615 31 076 Toulouse Cedex 3, France; University of Bolton, Institute for Materials Research and Innovation, Deane Road, Bolton, BL3 5AB Greater Manchester, UK.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Laouani
authors.affiliation: University of Bolton, Institute for Materials Research and Innovation, Deane Road, Bolton, BL3 5AB Greater Manchester, UK. Electronic address: s.halacheva@bolton.ac.uk.
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Halacheva
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D016627:Oxidopamine / Q000633:toxicity*; D011109:Polymethacrylic Acids / Q000008:administration & dosage* / Q000737:chemistry; D020011:Protective Agents / Q000008:administration & dosage* / Q000737:chemistry; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D011109:Polymethacrylic Acids; D020011:Protective Agents; C507106:poly(acrylic acid-co-methyl methacrylate); D016627:Oxidopamine; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D003474:Curcumin
keywords: Curcumin; Disulphide crosslinking; Hollow microspheres; Poly(methyl methacrylate-co-acrylic acid); Rat brain synaptosomes