title: Multifunctional PLGA particles containing poly(l-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity.
abstract: A water-soluble antioxidant (ascorbic acid, vitamin C) was encapsulated together with poly(l-glutamic acid)-capped silver nanoparticles (AgNpPGA) within a poly(lactide-co-glycolide) (PLGA) polymeric matrix and their synergistic effects were studied. The PLGA/AgNpPGA/ascorbic acid particles synthesized by a physicochemical method with solvent/non-solvent systems are spherical, have a mean diameter of 775 nm and a narrow size distribution with a polydispersity index of 0.158. The encapsulation efficiency of AgNpPGA/ascorbic acid within PLGA was determined to be >90%. The entire amount of encapsulated ascorbic acid was released in 68 days, and the entire amount of AgNpPGAs was released in 87 days of degradation. The influence of PLGA/AgNpPGA/ascorbic acid on cell viability, generation of reactive oxygen species (ROS) in HepG2 cells, as well as antimicrobial activity against seven different pathogens was investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated good biocompatibility of these PLGA/AgNpPGA/ascorbic acid particles. We measured the kinetics of ROS formation in HepG2 cells by a DCFH-DA assay, and found that PLGA/AgNpPGA/ascorbic acid caused a significant decrease in DCF fluorescence intensity, which was 2-fold lower than that in control cells after a 5h exposure. This indicates that the PLGA/AgNpPGA/ascorbic acid microspheres either act as scavengers of intracellular ROS and/or reduce their formation. Also, the results of antimicrobial activity of PLGA/AgNpPGA/ascorbic acid obtained by the broth microdilution method showed superior and extended activity of these particles. The samples were characterized using Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, zeta potential and particle size analysis. This paper presents a new approach to the treatment of infection that at the same time offers a very pronounced antioxidant effect.
authors.affiliation: Centre for Fine Particles Processing and Nanotechnologies, Institute of Technical Sciences of the Serbian Academy of Sciences and Arts, Knez Mihailova 35/IV, 11000 Belgrade, Serbia. Electronic address: magdalena.stevanovic@itn.sanu.ac.rs.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Stevanović
authors.forename: Ines
authors.initials: I
authors.lastname: Bračko
authors.forename: Marina
authors.initials: M
authors.lastname: Milenković
authors.forename: Nenad
authors.initials: N
authors.lastname: Filipović
authors.forename: Jana
authors.initials: J
authors.lastname: Nunić
authors.forename: Metka
authors.initials: M
authors.lastname: Filipič
authors.forename: Dragan P
authors.initials: DP
authors.lastname: Uskoković
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000737:chemistry*; D001419:Bacteria / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction / Q000187:drug effects; D011099:Polyglutamic Acid / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity
chemical_list: D000890:Anti-Infective Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011099:Polyglutamic Acid; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012834:Silver; D001205:Ascorbic Acid
keywords: Antimicrobial activity; Antioxidant; Biomedical applications; PLGA; Silver nanoparticles