Tomić, Sergej

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  • Tomić, Sergej (5)

Author's Bibliography

Frangula alnus ekstrakt i emodin kao potencijalni antikancerski agensi

Vuletić, Stefana; Cvetković, Stefana; Tomić, Nina; Ganić, Tea; Tomić, Sergej; Bekić, Marina; Nikolić, Biljana; Mitić Ćulafić, Dragana

(Beograd : Udruženje toksikologa Srbije, 2023)

TY  - CONF
AU  - Vuletić, Stefana
AU  - Cvetković, Stefana
AU  - Tomić, Nina
AU  - Ganić, Tea
AU  - Tomić, Sergej
AU  - Bekić, Marina
AU  - Nikolić, Biljana
AU  - Mitić Ćulafić, Dragana
PY  - 2023
UR  - https://dais.sanu.ac.rs/123456789/16247
AB  - Hepatocelularni i kolorektalni karcinom se sve ćešće javlja i ima visoku stopu smrtnosti. Postojanje aktivnih mehanizama hemorezistencije otežava korisnost hemoterapije. Upravo je pojava hemorezistencije podstakla opsežna istraživanja za razvoj novih terapeutskih agenasa i strategija za lečenje ovih vrsta karcinoma. Prirodni proizvodi biljnog porekla (sekundarni metaboliti) su bogat izvor potencijalnih lekova. Zbog toga smo u istraživanju usmerili pažnju na etil-acetatni ekstrakt biljke Frangula alnus (FA) i njegovu dominantnu komponentu emodin (E) i ispitali njihovo antikancerski potencijal na ćelijama hepatocelularnog (HepG2) i kolorektalnog (HCT116) karcinoma i citotoksičnost na normalnim MRC -5 ćelijama. Pokazan je snažan antioksidativni potencijal ekstrakta (DPPH i TBA test). Citotoksičnost ispitana MTT testom pokazala je jaku toksičnost obe supstance na ćelije HepG2 i HCT116, ali bez uticaja na MRC-5 ćelije. Dalje je analiza ćelijskog ciklusa pokazala da su i FA i E izazvali zaustavljanje u G1 fazi i blago nakupljanje ćelija u G2/M fazi. Pored toga, obe supstance su uvele ćelije u apoptozu i nekrozu i uticale su na mitohondrijalni membranski potencijal. Dalje, izazvali su značajan genotoksični efekat u kometnom testu na svim ćelijskim linijama. Može se zaključiti da su FA i E dobri kandidati za nove antikancerogene agense prirodnog porekla. Međutim, neophodna su dodatna istraživanja, posebno kada je u pitanju citotoksična aktivnost i bezbednost primene ovih supstanci.
AB  - Hepatocellular and colorectal carcinoma is swiftly increasing alongside a high mortality rate. The existence of active mechanisms of chemoresistance hampers the usefulness of chemotherapy. The emergence of chemoresistance encouraged extensive research to develop new therapeutic agents and strategies for the treatment of these types of cancer. Natural products of plant origin (secondary metabolites) have been the most successful source of potential drug leads. Therefore, we turned our attention to the Frangula alnus ethyl-acetate extract (FA) and its dominant constituent emodin (E) and explored them for their anticancer potential on hepatocellular (HepG2) and colorectal (HCT116) carcinoma cells, and cytotoxicity on normal MRC-5 cells. Strong antioxidant potential of the extract was demonstrated (DPPH and TBA test). Cytotoxicity investigated by the MTT assay showed strong cell toxicity of both substances on HepG2 and HCT116 cells, but without affecting MRC-5 cells. Next, the analysis of cell cycles exhibited that both FA and E induced arrest in the G1 phase and slight accumulation of cells in the G2/M phase. In addition, both substances introduced cells into apoptosis and necrosis and modulated mitochondrial membrane potential. Further on, they caused significant genotoxic effect in comet assay applied in all cell lines. It can be concluded that FA and E are good candidates for new anticancer agents of natural origin. However, additional studies are necessary, especially when it comes to the cytotoxic activity and safety of the application of these substances.
PB  - Beograd : Udruženje toksikologa Srbije
C3  - 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference : Present and future of toxicology: challenges and opportunities : 10-12 May 2023 Belgrade : abstract book, 2023
T1  - Frangula alnus ekstrakt i emodin kao potencijalni antikancerski agensi
T1  - Frangula alnus extract and emodin as potential anticancer agents
SP  - 148
EP  - 149
UR  - https://hdl.handle.net/21.15107/rcub_dais_16247
ER  - 
@conference{
author = "Vuletić, Stefana and Cvetković, Stefana and Tomić, Nina and Ganić, Tea and Tomić, Sergej and Bekić, Marina and Nikolić, Biljana and Mitić Ćulafić, Dragana",
year = "2023",
abstract = "Hepatocelularni i kolorektalni karcinom se sve ćešće javlja i ima visoku stopu smrtnosti. Postojanje aktivnih mehanizama hemorezistencije otežava korisnost hemoterapije. Upravo je pojava hemorezistencije podstakla opsežna istraživanja za razvoj novih terapeutskih agenasa i strategija za lečenje ovih vrsta karcinoma. Prirodni proizvodi biljnog porekla (sekundarni metaboliti) su bogat izvor potencijalnih lekova. Zbog toga smo u istraživanju usmerili pažnju na etil-acetatni ekstrakt biljke Frangula alnus (FA) i njegovu dominantnu komponentu emodin (E) i ispitali njihovo antikancerski potencijal na ćelijama hepatocelularnog (HepG2) i kolorektalnog (HCT116) karcinoma i citotoksičnost na normalnim MRC -5 ćelijama. Pokazan je snažan antioksidativni potencijal ekstrakta (DPPH i TBA test). Citotoksičnost ispitana MTT testom pokazala je jaku toksičnost obe supstance na ćelije HepG2 i HCT116, ali bez uticaja na MRC-5 ćelije. Dalje je analiza ćelijskog ciklusa pokazala da su i FA i E izazvali zaustavljanje u G1 fazi i blago nakupljanje ćelija u G2/M fazi. Pored toga, obe supstance su uvele ćelije u apoptozu i nekrozu i uticale su na mitohondrijalni membranski potencijal. Dalje, izazvali su značajan genotoksični efekat u kometnom testu na svim ćelijskim linijama. Može se zaključiti da su FA i E dobri kandidati za nove antikancerogene agense prirodnog porekla. Međutim, neophodna su dodatna istraživanja, posebno kada je u pitanju citotoksična aktivnost i bezbednost primene ovih supstanci., Hepatocellular and colorectal carcinoma is swiftly increasing alongside a high mortality rate. The existence of active mechanisms of chemoresistance hampers the usefulness of chemotherapy. The emergence of chemoresistance encouraged extensive research to develop new therapeutic agents and strategies for the treatment of these types of cancer. Natural products of plant origin (secondary metabolites) have been the most successful source of potential drug leads. Therefore, we turned our attention to the Frangula alnus ethyl-acetate extract (FA) and its dominant constituent emodin (E) and explored them for their anticancer potential on hepatocellular (HepG2) and colorectal (HCT116) carcinoma cells, and cytotoxicity on normal MRC-5 cells. Strong antioxidant potential of the extract was demonstrated (DPPH and TBA test). Cytotoxicity investigated by the MTT assay showed strong cell toxicity of both substances on HepG2 and HCT116 cells, but without affecting MRC-5 cells. Next, the analysis of cell cycles exhibited that both FA and E induced arrest in the G1 phase and slight accumulation of cells in the G2/M phase. In addition, both substances introduced cells into apoptosis and necrosis and modulated mitochondrial membrane potential. Further on, they caused significant genotoxic effect in comet assay applied in all cell lines. It can be concluded that FA and E are good candidates for new anticancer agents of natural origin. However, additional studies are necessary, especially when it comes to the cytotoxic activity and safety of the application of these substances.",
publisher = "Beograd : Udruženje toksikologa Srbije",
journal = "13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference : Present and future of toxicology: challenges and opportunities : 10-12 May 2023 Belgrade : abstract book, 2023",
title = "Frangula alnus ekstrakt i emodin kao potencijalni antikancerski agensi, Frangula alnus extract and emodin as potential anticancer agents",
pages = "148-149",
url = "https://hdl.handle.net/21.15107/rcub_dais_16247"
}
Vuletić, S., Cvetković, S., Tomić, N., Ganić, T., Tomić, S., Bekić, M., Nikolić, B.,& Mitić Ćulafić, D.. (2023). Frangula alnus ekstrakt i emodin kao potencijalni antikancerski agensi. in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference : Present and future of toxicology: challenges and opportunities : 10-12 May 2023 Belgrade : abstract book, 2023
Beograd : Udruženje toksikologa Srbije., 148-149.
https://hdl.handle.net/21.15107/rcub_dais_16247
Vuletić S, Cvetković S, Tomić N, Ganić T, Tomić S, Bekić M, Nikolić B, Mitić Ćulafić D. Frangula alnus ekstrakt i emodin kao potencijalni antikancerski agensi. in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference : Present and future of toxicology: challenges and opportunities : 10-12 May 2023 Belgrade : abstract book, 2023. 2023;:148-149.
https://hdl.handle.net/21.15107/rcub_dais_16247 .
Vuletić, Stefana, Cvetković, Stefana, Tomić, Nina, Ganić, Tea, Tomić, Sergej, Bekić, Marina, Nikolić, Biljana, Mitić Ćulafić, Dragana, "Frangula alnus ekstrakt i emodin kao potencijalni antikancerski agensi" in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference : Present and future of toxicology: challenges and opportunities : 10-12 May 2023 Belgrade : abstract book, 2023 (2023):148-149,
https://hdl.handle.net/21.15107/rcub_dais_16247 .

Toxicity of nanostructures

Čolić, Miodrag; Tomić, Sergej

(Belgrade : SASA, 2020)

TY  - CONF
AU  - Čolić, Miodrag
AU  - Tomić, Sergej
PY  - 2020
UR  - https://dais.sanu.ac.rs/123456789/9247
AB  - Due to their unique size (dimensions of 1 to 100 nm) and
physicochemical properties, nanomaterials have found numerous applications in
electronics, cosmetics, household appliances, energy storage, food industry, pharmacy and medicine. However, increased production of nanomaterials raises concern about their safety, not only for human beings but also for animals and the
environment. Numerous studies confirmed that nanoparticles (NPs) can exert
toxicity both, in vitro and in vivo, depending on their size, shape, surface area,
surface chemistry, concentration, dispersion, aggregation, route of administration
and many other factors, all of which are also relevant to desired biological properties of nanostructures. This review summarizes the main aspects of nanotoxicity in
vitro and in vivo, points out relevant tests in order to demonstrate the toxicity and
explains the significance of reactive oxygen species, as the main triggering factor
of NP cytotoxicity and genotoxicity, acting through the complex interplay between
NPs and cellular or genomic components, respectively. Special attention was devoted to the immunotoxic and immunomodulatory properties of NPs and their
relevance for production of less immunogenic nanostructures capable of avoiding
undesirable immune responses and the use of NPs as specific nanotherapeutics
for drug delivery and vaccination strategy. Finally, ecotoxicological aspects of NPs
are presented, showing why aquatic ecosystems are the most susceptible to environmental contamination and why studies on aquatic organisms are important for
translational nanotoxicology.
AB  - Због своје јединствене величине (димензије од 1 до 100 нм) и физичко-хемијских својстава, наноматеријали су нашли бројне примене у електроници, козметици, кућним апаратима, складиштењу енергије, прехрамбеној
индустрији, фармацији и медицини. Међутим, повећана производња наноматеријала изазива забринутост у погледу њихове сигурности, не само за
људска бића, већ и за животиње и животну средину. Бројна истраживања су
потврдила да наночестице (НЧ) могу да испољавају токсичност, in vitro и in
vivo, која зависи од њихове величине, облика, површине, хемијског састава
површине, концентрације, степена дисперзије и агрегације, начина примене
и многих других фактора. Сваки од њих је релевантан за очекивано биолошко својство одређене наноструктуре. Овај прегледни чланак приказује
сажето главне аспекте нанотоксичности in vitro и in vivo и истиче битне тестове којима се доказује токсичност НЧ. Посебно се наглашава значај реактивних врста кисеоника, као главног покретачког фактора цитотоксичности
и генотоксичности НЧ, које делују у сложеној међусобној интеракцији НЧ
са ћелијским, односно геномским компонентама. Посебан аспект се односи на имунотоксична и имуномодулацијска својства НЧ, што је од велике
важности за производњу мање имуногених наноструктура. На тај начин се може избећи нежељени имунски одговор и омогућити примена НЧ као
специфичних нанотерапеутика за доставу лекова и развој нових стратегија
вакцинације. На крају су приказани екотоксиколошки аспекти НЧ, указано
је зашто су водени екосистеми најосетљивији када се разматра контаминација животне средине наночестицама и зашто су истраживања на воденим
организмима важнa за област транслацијске нанотоксикологије.
PB  - Belgrade : SASA
C3  - Fascinating world of nanoscience and nanotechnology
T1  - Toxicity of nanostructures
T1  - Токсичност наноструктура
SP  - 71
EP  - 122
UR  - https://hdl.handle.net/21.15107/rcub_dais_9247
ER  - 
@conference{
author = "Čolić, Miodrag and Tomić, Sergej",
year = "2020",
abstract = "Due to their unique size (dimensions of 1 to 100 nm) and
physicochemical properties, nanomaterials have found numerous applications in
electronics, cosmetics, household appliances, energy storage, food industry, pharmacy and medicine. However, increased production of nanomaterials raises concern about their safety, not only for human beings but also for animals and the
environment. Numerous studies confirmed that nanoparticles (NPs) can exert
toxicity both, in vitro and in vivo, depending on their size, shape, surface area,
surface chemistry, concentration, dispersion, aggregation, route of administration
and many other factors, all of which are also relevant to desired biological properties of nanostructures. This review summarizes the main aspects of nanotoxicity in
vitro and in vivo, points out relevant tests in order to demonstrate the toxicity and
explains the significance of reactive oxygen species, as the main triggering factor
of NP cytotoxicity and genotoxicity, acting through the complex interplay between
NPs and cellular or genomic components, respectively. Special attention was devoted to the immunotoxic and immunomodulatory properties of NPs and their
relevance for production of less immunogenic nanostructures capable of avoiding
undesirable immune responses and the use of NPs as specific nanotherapeutics
for drug delivery and vaccination strategy. Finally, ecotoxicological aspects of NPs
are presented, showing why aquatic ecosystems are the most susceptible to environmental contamination and why studies on aquatic organisms are important for
translational nanotoxicology., Због своје јединствене величине (димензије од 1 до 100 нм) и физичко-хемијских својстава, наноматеријали су нашли бројне примене у електроници, козметици, кућним апаратима, складиштењу енергије, прехрамбеној
индустрији, фармацији и медицини. Међутим, повећана производња наноматеријала изазива забринутост у погледу њихове сигурности, не само за
људска бића, већ и за животиње и животну средину. Бројна истраживања су
потврдила да наночестице (НЧ) могу да испољавају токсичност, in vitro и in
vivo, која зависи од њихове величине, облика, површине, хемијског састава
површине, концентрације, степена дисперзије и агрегације, начина примене
и многих других фактора. Сваки од њих је релевантан за очекивано биолошко својство одређене наноструктуре. Овај прегледни чланак приказује
сажето главне аспекте нанотоксичности in vitro и in vivo и истиче битне тестове којима се доказује токсичност НЧ. Посебно се наглашава значај реактивних врста кисеоника, као главног покретачког фактора цитотоксичности
и генотоксичности НЧ, које делују у сложеној међусобној интеракцији НЧ
са ћелијским, односно геномским компонентама. Посебан аспект се односи на имунотоксична и имуномодулацијска својства НЧ, што је од велике
важности за производњу мање имуногених наноструктура. На тај начин се може избећи нежељени имунски одговор и омогућити примена НЧ као
специфичних нанотерапеутика за доставу лекова и развој нових стратегија
вакцинације. На крају су приказани екотоксиколошки аспекти НЧ, указано
је зашто су водени екосистеми најосетљивији када се разматра контаминација животне средине наночестицама и зашто су истраживања на воденим
организмима важнa за област транслацијске нанотоксикологије.",
publisher = "Belgrade : SASA",
journal = "Fascinating world of nanoscience and nanotechnology",
title = "Toxicity of nanostructures, Токсичност наноструктура",
pages = "71-122",
url = "https://hdl.handle.net/21.15107/rcub_dais_9247"
}
Čolić, M.,& Tomić, S.. (2020). Toxicity of nanostructures. in Fascinating world of nanoscience and nanotechnology
Belgrade : SASA., 71-122.
https://hdl.handle.net/21.15107/rcub_dais_9247
Čolić M, Tomić S. Toxicity of nanostructures. in Fascinating world of nanoscience and nanotechnology. 2020;:71-122.
https://hdl.handle.net/21.15107/rcub_dais_9247 .
Čolić, Miodrag, Tomić, Sergej, "Toxicity of nanostructures" in Fascinating world of nanoscience and nanotechnology (2020):71-122,
https://hdl.handle.net/21.15107/rcub_dais_9247 .

Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles

Filipović, Nenad; Veselinović, Ljiljana; Ražić, Slavica; Jeremić, Sanja; Filipič, Metka; Žegura, Bojana; Tomić, Sergej; Čolić, Miodrag; Stevanović, Magdalena

(Elsevier, 2019)

TY  - JOUR
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipič, Metka
AU  - Žegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://dais.sanu.ac.rs/123456789/4600
AB  - Poly (ε-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 μm 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. © 2018 Elsevier B.V.
PB  - Elsevier
T2  - Materials Science and Engineering C
T1  - Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles
SP  - 776
EP  - 789
VL  - 96
DO  - 10.1016/j.msec.2018.11.073
UR  - https://hdl.handle.net/21.15107/rcub_dais_4600
ER  - 
@article{
author = "Filipović, Nenad and Veselinović, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipič, Metka and Žegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "Poly (ε-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 μm 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. © 2018 Elsevier B.V.",
publisher = "Elsevier",
journal = "Materials Science and Engineering C",
title = "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles",
pages = "776-789",
volume = "96",
doi = "10.1016/j.msec.2018.11.073",
url = "https://hdl.handle.net/21.15107/rcub_dais_4600"
}
Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C
Elsevier., 96, 776-789.
https://doi.org/10.1016/j.msec.2018.11.073
https://hdl.handle.net/21.15107/rcub_dais_4600
Filipović N, Veselinović L, Ražić S, Jeremić S, Filipič M, Žegura B, Tomić S, Čolić M, Stevanović M. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C. 2019;96:776-789.
doi:10.1016/j.msec.2018.11.073
https://hdl.handle.net/21.15107/rcub_dais_4600 .
Filipović, Nenad, Veselinović, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipič, Metka, Žegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles" in Materials Science and Engineering C, 96 (2019):776-789,
https://doi.org/10.1016/j.msec.2018.11.073 .,
https://hdl.handle.net/21.15107/rcub_dais_4600 .
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Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles

Filipović, Nenad; Veselinović, Ljiljana; Ražić, Slavica; Jeremić, Sanja; Filipič, Metka; Žegura, Bojana; Tomić, Sergej; Čolić, Miodrag; Stevanović, Magdalena

(Elsevier, 2019)

TY  - JOUR
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipič, Metka
AU  - Žegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://dais.sanu.ac.rs/123456789/4590
AB  - Poly (ε-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 μm 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. © 2018 Elsevier B.V.
PB  - Elsevier
T2  - Materials Science and Engineering C
T1  - Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles
SP  - 776
EP  - 789
VL  - 96
DO  - 10.1016/j.msec.2018.11.073
UR  - https://hdl.handle.net/21.15107/rcub_dais_4590
ER  - 
@article{
author = "Filipović, Nenad and Veselinović, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipič, Metka and Žegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "Poly (ε-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 μm 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. © 2018 Elsevier B.V.",
publisher = "Elsevier",
journal = "Materials Science and Engineering C",
title = "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles",
pages = "776-789",
volume = "96",
doi = "10.1016/j.msec.2018.11.073",
url = "https://hdl.handle.net/21.15107/rcub_dais_4590"
}
Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C
Elsevier., 96, 776-789.
https://doi.org/10.1016/j.msec.2018.11.073
https://hdl.handle.net/21.15107/rcub_dais_4590
Filipović N, Veselinović L, Ražić S, Jeremić S, Filipič M, Žegura B, Tomić S, Čolić M, Stevanović M. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C. 2019;96:776-789.
doi:10.1016/j.msec.2018.11.073
https://hdl.handle.net/21.15107/rcub_dais_4590 .
Filipović, Nenad, Veselinović, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipič, Metka, Žegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles" in Materials Science and Engineering C, 96 (2019):776-789,
https://doi.org/10.1016/j.msec.2018.11.073 .,
https://hdl.handle.net/21.15107/rcub_dais_4590 .
1
23
13
23

Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073

Filipović, Nenad; Veselinović, Ljiljana; Ražić, Slavica; Jeremić, Sanja; Filipič, Metka; Žegura, Bojana; Tomić, Sergej; Čolić, Miodrag; Stevanović, Magdalena

(2019)

TY  - DATA
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipič, Metka
AU  - Žegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://dais.sanu.ac.rs/123456789/5972
AB  - 1. Experimental details for ICP-OES measurements; 1.1. Instrumental and operating conditions; 1.2.Solutions and Reagents; 1.3. Microwave assisted acid digestion; 1.4. Calibration curve 2. Experimental details for biocompatibility investigations of PCL/SeNPs; 2.1. Cell culture; 2.2.Determining citotoxicity of samples - MTT assay; 2.3. Determination of intracellular reactive oxygen species formation – DCFH-DA assay; 2.4. DNA damage (comet assay) Figure 1. SEM image of blank PCL microspheres Figure 2. XRD pattern of commercial PGA used in experiments Figure 3. Interaction with PCL/SeNPs in vivo by infiltrating cells. PCL/SeNPs (4mg/animal) were injected into sterile polyvinyl sponges implanted subcutaneously. The infiltrating cells were collected from the sponges after 3h and stained to anti-CD45/IgG Alexa 488 (Green) and Syto59 nuclear stain. PCL/SeNPs were detected as brightly scattering particles sized about 1-4 μm after 546nm laser excitation either intracellularly within granulocytes (A) or extracellularly (B). Note that some cells expressed strongly CD45 on the membrane and the cytoplasm, whereas others displayed a weak membrane expression and a strong expression in the granular ER at the nucleus level. Table 1. Melting temperatures Tm and corresponding enthalpies (heat) of fusion ΔHf of PCL/SeNPs samples taken after different time from different degradation mediums Table 2. Melting temperatures and corresponding enthalpies of PCL/SeNPs samples taken after different degradation periods from P. aeruginosa CFE medium
T2  - Materials Science and Engineering C
T1  - Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073
UR  - https://hdl.handle.net/21.15107/rcub_dais_5972
ER  - 
@misc{
author = "Filipović, Nenad and Veselinović, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipič, Metka and Žegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "1. Experimental details for ICP-OES measurements; 1.1. Instrumental and operating conditions; 1.2.Solutions and Reagents; 1.3. Microwave assisted acid digestion; 1.4. Calibration curve 2. Experimental details for biocompatibility investigations of PCL/SeNPs; 2.1. Cell culture; 2.2.Determining citotoxicity of samples - MTT assay; 2.3. Determination of intracellular reactive oxygen species formation – DCFH-DA assay; 2.4. DNA damage (comet assay) Figure 1. SEM image of blank PCL microspheres Figure 2. XRD pattern of commercial PGA used in experiments Figure 3. Interaction with PCL/SeNPs in vivo by infiltrating cells. PCL/SeNPs (4mg/animal) were injected into sterile polyvinyl sponges implanted subcutaneously. The infiltrating cells were collected from the sponges after 3h and stained to anti-CD45/IgG Alexa 488 (Green) and Syto59 nuclear stain. PCL/SeNPs were detected as brightly scattering particles sized about 1-4 μm after 546nm laser excitation either intracellularly within granulocytes (A) or extracellularly (B). Note that some cells expressed strongly CD45 on the membrane and the cytoplasm, whereas others displayed a weak membrane expression and a strong expression in the granular ER at the nucleus level. Table 1. Melting temperatures Tm and corresponding enthalpies (heat) of fusion ΔHf of PCL/SeNPs samples taken after different time from different degradation mediums Table 2. Melting temperatures and corresponding enthalpies of PCL/SeNPs samples taken after different degradation periods from P. aeruginosa CFE medium",
journal = "Materials Science and Engineering C",
title = "Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073",
url = "https://hdl.handle.net/21.15107/rcub_dais_5972"
}
Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073. in Materials Science and Engineering C.
https://hdl.handle.net/21.15107/rcub_dais_5972
Filipović N, Veselinović L, Ražić S, Jeremić S, Filipič M, Žegura B, Tomić S, Čolić M, Stevanović M. Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073. in Materials Science and Engineering C. 2019;.
https://hdl.handle.net/21.15107/rcub_dais_5972 .
Filipović, Nenad, Veselinović, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipič, Metka, Žegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073" in Materials Science and Engineering C (2019),
https://hdl.handle.net/21.15107/rcub_dais_5972 .