title: Composite PLGA/AgNpPGA/AscH nanospheres with combined osteoinductive, antioxidative, and antimicrobial activities.
abstract: The global rise in the resistance of pathogens to conventional antibiotics has created an intensive search for alternative materials with antimicrobial properties. This study is performed with an intention to investigate the combined effects of poly(l-glutamic acid)-capped silver nanoparticles (AgNpPGA) and ascorbic acid (AscH) encapsulated within freeze-dried poly(lactide-co-glycolide) (PLGA) nanospheres to obtain a nanomaterial with simultaneous osteoinductive, antioxidative, and prolonged antimicrobial properties. The influence of PLGA/AgNpPGA/AscH particles on (i) viability and superoxide production of human umbilical vein endothelial cells in vitro, (ii) morphology and expression of osteogenic markers in osteoblastic MC3T3-E1 cells in vitro, and (iii) antimicrobial activity against a Gram-positive bacterium, methicillin-resistant Staphylococcus aureus, and a Gram-negative bacterium, Escherichia coli, was investigated. PLGA/AgNpPGA/AscH nanoparticles showed a superior and extended antibacterial activity against both types of bacteria. The nanoparticles appeared to be capable of delivering ascorbate to the cells, which was evidenced by the significant decrease in the level of superoxides in human umbilical vein endothelial cells and which could have a therapeutic potential in preventing oxidative stress. PLGA/AgNpPGA/AscH nanoparticles had a positive effect on MC3T3-E1 osteoblastic cells in vitro, promoting: (i) an intimate contact with the cells and preservation of their healthy morphologies; (ii) unreduced cell viability; and (iii) multiple-fold upregulation of two osteogenic markers: osteocalcin and type I procollagen. It is concluded that PLGA/AgNpPGA/AscH nanospheres present a promising new material for the treatment of infections and use in wound dressings and other prophylactic applications.
authors.affiliation: Institute of Technical Sciences of the Serbian Academy of Sciences and Arts , 11000 Belgrade, Serbia.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Stevanović
authors.forename: Vuk
authors.initials: V
authors.lastname: Uskoković
authors.forename: Miloš
authors.initials: M
authors.lastname: Filipović
authors.forename: Srečo D
authors.initials: SD
authors.lastname: Škapin
authors.forename: Dragan
authors.initials: D
authors.lastname: Uskoković
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D001205:Ascorbic Acid / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D054118:Nanospheres / Q000737:chemistry*; D010012:Osteogenesis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012834:Silver / Q000737:chemistry*; D013481:Superoxides / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D000975:Antioxidants; D013481:Superoxides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012834:Silver; D001205:Ascorbic Acid