TY  - JOUR
AU  - Filipović, Nenad
AU  - Veselinovic, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipić, Metka
AU  - Zegura, Bojana
AU  - Tomic, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3328
AB  - Poly (e-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1-4 mu m with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants.
PB  - Elsevier Science BV, Amsterdam
T2  - Materials Science & Engineering C: Materials for Biological Applications
T1  - Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles
VL  - 96
SP  - 776
EP  - 789
DO  - 10.1016/j.msec.2018.11.073
ER  - 

@article{
author = "Filipović, Nenad and Veselinovic, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipić, Metka and Zegura, Bojana and Tomic, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "Poly (e-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1-4 mu m with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Materials Science & Engineering C: Materials for Biological Applications",
title = "Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles",
volume = "96",
pages = "776-789",
doi = "10.1016/j.msec.2018.11.073"
}

Filipović, N., Veselinovic, L., Ražić, S., Jeremić, S., Filipić, M., Zegura, B., Tomic, S., Čolić, M.,& Stevanović, M.. (2019). Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science & Engineering C: Materials for Biological Applications
Elsevier Science BV, Amsterdam., 96, 776-789.
https://doi.org/10.1016/j.msec.2018.11.073

Filipović N, Veselinovic L, Ražić S, Jeremić S, Filipić M, Zegura B, Tomic S, Čolić M, Stevanović M. Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science & Engineering C: Materials for Biological Applications. 2019;96:776-789.
doi:10.1016/j.msec.2018.11.073 .

Filipović, Nenad, Veselinovic, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipić, Metka, Zegura, Bojana, Tomic, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Poly (epsilon-caprolactone) microspheres for prolonged release of selenium nanoparticles" in Materials Science & Engineering C: Materials for Biological Applications, 96 (2019):776-789,
https://doi.org/10.1016/j.msec.2018.11.073 . .

TY  - JOUR
AU  - Stevanović, Magdalena
AU  - Bracko, Ines
AU  - Milenković, Marina
AU  - Filipović, Nenad
AU  - Nunić, Jana
AU  - Filipić, Metka
AU  - Uskoković, Dragan P.
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2184
AB  - 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 5 h 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.
PB  - Elsevier Sci Ltd, Oxford
T2  - Acta Biomaterialia
T1  - Multifunctional PLGA particles containing poly(L-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity
VL  - 10
IS  - 1
SP  - 151
EP  - 162
DO  - 10.1016/j.actbio.2013.08.030
ER  - 

@article{
author = "Stevanović, Magdalena and Bracko, Ines and Milenković, Marina and Filipović, Nenad and Nunić, Jana and Filipić, Metka and Uskoković, Dragan P.",
year = "2014",
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 5 h 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.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Acta Biomaterialia",
title = "Multifunctional PLGA particles containing poly(L-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity",
volume = "10",
number = "1",
pages = "151-162",
doi = "10.1016/j.actbio.2013.08.030"
}

Stevanović, M., Bracko, I., Milenković, M., Filipović, N., Nunić, J., Filipić, M.,& Uskoković, D. P.. (2014). Multifunctional PLGA particles containing poly(L-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity. in Acta Biomaterialia
Elsevier Sci Ltd, Oxford., 10(1), 151-162.
https://doi.org/10.1016/j.actbio.2013.08.030

Stevanović M, Bracko I, Milenković M, Filipović N, Nunić J, Filipić M, Uskoković DP. Multifunctional PLGA particles containing poly(L-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity. in Acta Biomaterialia. 2014;10(1):151-162.
doi:10.1016/j.actbio.2013.08.030 .

Stevanović, Magdalena, Bracko, Ines, Milenković, Marina, Filipović, Nenad, Nunić, Jana, Filipić, Metka, Uskoković, Dragan P., "Multifunctional PLGA particles containing poly(L-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity" in Acta Biomaterialia, 10, no. 1 (2014):151-162,
https://doi.org/10.1016/j.actbio.2013.08.030 . .

TY  - JOUR
AU  - Stevanović, Magdalena
AU  - Skapin, Sreco D.
AU  - Bracko, Ines
AU  - Milenković, Marina
AU  - Petković, Jana
AU  - Filipić, Metka
AU  - Uskoković, Dragan P.
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1733
AB  - Silver nanoparticles (AgNps) were prepared by modified chemical reduction with poly (alpha, gamma, L-glutamic acid) (PGA) as capping agent. These Ag/PGA nanoparticles (AgNpPGAs) were highly stable over long periods of time without signs of precipitation. In addition to obtaining stable AgNpPGAs, a further aim was to examine their encapsulation in the poly(L-lactide-co-glycolide) (PLGA) polymer matrix. The current interest of polymer-AgNps in biomedical applications is because a versatile system must have antimicrobial activity upon target contact, without the release of toxic biocides. The synthesis of these PLGA/AgNpPGAs used physicochemical methods with solvent/non-solvent systems. Degradation of these PLGA/AgNpPGAs and the release rate of their AgNPs were studied in physiological solution over three months. The antimicrobial activity of the samples was investigated towards six laboratory control strains from the American Type Culture Collection (ATCC) and one clinical isolate methicillin-resistant Staphylococcus aureus strain by the broth microdilution method and the results showed superior and extended activity of PLGA/AgNpPGAs. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated good biocompatibility of these PLGA/AgNpPGAs. The formation of intracellular reactive oxygen species was measured spectrophotometrically using a fluorescent probe, which showed that these PLGA/AgNpPGAs are not inducers of such species. The samples were characterized by UV-VIS spectrometry, X-ray diffraction, zeta potential measurements, field-emission scanning electron microscopy, and transmission electron microscopy.
PB  - Elsevier Sci Ltd, Oxford
T2  - Polymer
T1  - Poly(lactide-co-glycolide)/silver nanoparticles: Synthesis, characterization, antimicrobial activity, cytotoxicity assessment and ROS-inducing potential
VL  - 53
IS  - 14
SP  - 2818
EP  - 2828
DO  - 10.1016/j.polymer.2012.04.057
ER  - 

@article{
author = "Stevanović, Magdalena and Skapin, Sreco D. and Bracko, Ines and Milenković, Marina and Petković, Jana and Filipić, Metka and Uskoković, Dragan P.",
year = "2012",
abstract = "Silver nanoparticles (AgNps) were prepared by modified chemical reduction with poly (alpha, gamma, L-glutamic acid) (PGA) as capping agent. These Ag/PGA nanoparticles (AgNpPGAs) were highly stable over long periods of time without signs of precipitation. In addition to obtaining stable AgNpPGAs, a further aim was to examine their encapsulation in the poly(L-lactide-co-glycolide) (PLGA) polymer matrix. The current interest of polymer-AgNps in biomedical applications is because a versatile system must have antimicrobial activity upon target contact, without the release of toxic biocides. The synthesis of these PLGA/AgNpPGAs used physicochemical methods with solvent/non-solvent systems. Degradation of these PLGA/AgNpPGAs and the release rate of their AgNPs were studied in physiological solution over three months. The antimicrobial activity of the samples was investigated towards six laboratory control strains from the American Type Culture Collection (ATCC) and one clinical isolate methicillin-resistant Staphylococcus aureus strain by the broth microdilution method and the results showed superior and extended activity of PLGA/AgNpPGAs. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated good biocompatibility of these PLGA/AgNpPGAs. The formation of intracellular reactive oxygen species was measured spectrophotometrically using a fluorescent probe, which showed that these PLGA/AgNpPGAs are not inducers of such species. The samples were characterized by UV-VIS spectrometry, X-ray diffraction, zeta potential measurements, field-emission scanning electron microscopy, and transmission electron microscopy.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Polymer",
title = "Poly(lactide-co-glycolide)/silver nanoparticles: Synthesis, characterization, antimicrobial activity, cytotoxicity assessment and ROS-inducing potential",
volume = "53",
number = "14",
pages = "2818-2828",
doi = "10.1016/j.polymer.2012.04.057"
}

Stevanović, M., Skapin, S. D., Bracko, I., Milenković, M., Petković, J., Filipić, M.,& Uskoković, D. P.. (2012). Poly(lactide-co-glycolide)/silver nanoparticles: Synthesis, characterization, antimicrobial activity, cytotoxicity assessment and ROS-inducing potential. in Polymer
Elsevier Sci Ltd, Oxford., 53(14), 2818-2828.
https://doi.org/10.1016/j.polymer.2012.04.057

Stevanović M, Skapin SD, Bracko I, Milenković M, Petković J, Filipić M, Uskoković DP. Poly(lactide-co-glycolide)/silver nanoparticles: Synthesis, characterization, antimicrobial activity, cytotoxicity assessment and ROS-inducing potential. in Polymer. 2012;53(14):2818-2828.
doi:10.1016/j.polymer.2012.04.057 .

Stevanović, Magdalena, Skapin, Sreco D., Bracko, Ines, Milenković, Marina, Petković, Jana, Filipić, Metka, Uskoković, Dragan P., "Poly(lactide-co-glycolide)/silver nanoparticles: Synthesis, characterization, antimicrobial activity, cytotoxicity assessment and ROS-inducing potential" in Polymer, 53, no. 14 (2012):2818-2828,
https://doi.org/10.1016/j.polymer.2012.04.057 . .