TY  - CONF
AU  - Obradović, Bojana
AU  - Stojkovska, Jasmina
AU  - Osmokrović, Andrea
AU  - Mišković Stanković, Vesna
AU  - Jančić, Ivan
AU  - Milenković, Marina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4666
AB  - Alginate hydrogels are widely used in wound dressings due to hydrophilicity, biocompatibility,
flexibility, and high sorption capacity, providing effective moisture regulation in wounds and inducing
rapid granulation and reepithelization of the damaged tissue. However, these dressings are not
bioactive so that different methodologies have been investigated to extend functionality of alginate
hydrogels.
In the present work, we show several approaches to achieve this aim by addition of different
biologically active components. These include incorporation of silver nanoparticles as potent
antimicrobial agents (1), bioactive honey components (2), activated charcoal (AC) particles as carriers
of therapeutically active agents (3) as well as the use of Zn-alginate hydrogels that release zinc ions (4).
The obtained composites were comprehensively characterized regarding composition, cytotoxicity,
antibacterial activity, release kinetics of active agents and wound treatment in a rat model.
Ag/alginate nanocomposite hydrogels releasing silver ions and/or nanoparticles exhibited high
bactericidal activity against a broad spectrum of standard and multi-drug resistant clinical bacterial
strains (Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus – MRSA,
Acinetobacter baumannii and Pseudomonas aeruginosa). Especially interesting results were obtained
against 13 clinical isolates of A. baumannii, which were completely extinguished over 48 h in 6 cases
(2). However, in 3 clinical isolates, antibacterial effects were not noticed implying possibility for
development of bacterial resistance to silver. In the treatment of 2nd degree burns in rats Ag/alginate
nanocomposites exhibited the same efficiency as commercial medical products (5).
Composite alginate hydrogels with immobilized AC particles impregnated with povidone iodine
(PVP-I) as a model therapeutically active agent, were developed with the aim to provide controlled
particle release in the wound without actually releasing the adsorbed substance, thus achieving the
desired activity without adverse effects by systemic absorption. The composite Ca-alginate hydrogels
induced strong bactericidal effects against two standard bacterial strains and clinical multi-resistant
wound isolates (MRSA, E. coli, P. aeruginosa, Еnterococcus faecalis and Proteus mirabilis) without
releasing PVP-I in the environment (3). Furthermore, composite Zn-alginate hydrogels released zinc
ions in addition to AC particles with adsorbed PVP-I, which induced additional microbicidal effects on
one wild yeast strain (Candida albicans). The obtained bactericidal effects were ascribed to effective
adsorption of bacteria onto AC particles and further direct contact with the adsorbed iodine, while the
antifungal activity against C. albicans was assigned to released Zn 2+.
Overall, the developed composite alginate hydrogels have shown high potentials for utilization
in variety of multifunctional wound dressings according to the specific needs.
AB  - Alginatni hidrogelovi se široko koriste u oblogama za rane zbog svoje hidrofilnosti,
biokompatibilnosti, fleksibilnosti i velikog sorpcionog kapaciteta čime obezbeđuju efikasnu regulaciju
vlažnosti rane i podstiču brzu granulaciju i reepitelizaciju oštećenog tkiva. Međutim, ove obloge nisu
bioaktivne tako da su istraživane različite metodologije kako bi se proširila funkcionalnost alginatnih
hidrogelova.
U ovom radu je prikazano nekoliko pristupa ostvarivanju tog cilja dodatkom različitih biološki
aktivnih komponenata. Ovi pristupi uključuju inkorporaciju nanočestica srebra kao potentnog
antimikrobnog agensa (1), bioaktivnih komponenata meda (2), čestica aktivnog uglja (AU) kao nosača
terapeutski aktivnih agenasa (3), kao i primenu hidrogelova Zn-alginata koji otpuštaju jone cinka.
Dobijeni kompoziti su sveobuhvatno karakterisani u pogledu sastava, citotoksičnosti, antibakterijske
aktivnosti, kinetike otpuštanja aktivnih agenasa i tretmana rana u eksperimentalnom modelu
opekotina na pacovima.
Ag/alginatni nanokompozitni hydrogelovi su usled otpuštanja jona i/ili nanočestica srebra,
pokazali izraženu baktericidnu aktivnost prema širokom spektru standardnih i kliničkih multi-
rezistentnih bakterijskih sojeva (Escherichia coli, Staphylococcus aureus, meticilin-resistentni
Staphylococcus aureus – MRSA, Acinetobacter baumannii i Pseudomonas aeruginosa). Posebno
interesantni rezultati su dobijeni u kulturama 13 kliničkih izolata A. baumannii, gde je u 6 slučajeva
postignut potpun baktericidan efekat u toku 48 h (2). Ipak, kod 3 klinička izolata nije postignuto
antibakterijsko dejstvo što ukazuje na mogućnost razvoja bakterijske rezistencije na srebro. U
tretmanu opekotina drugog stepena na pacovima, Ag/alginatni nanokompoziti su pokazali istu
efikasnost kao komercijalni medicinski proizvodi.
Kompozitni alginatni hidrogelovi sa imobilisanim česticama AU impregniranih povidon-jodom
kao model terapeutski aktivnom komponentom, su razvijeni sa ciljem da obezbede kontrolisano
otpuštanje čestica AU u rani bez otpuštanja adsorbovane supstance kako bi se na taj način postiglo
željeno dejstvo bez neželjenih efekata sistemske apsorpcije. Kompozitni Ca-alginatni hidrogelovi su
pokazali jake baktericidne efekte na dva standardna bakterijska soja i nekoliko kliničkih multi-
rezistentnih izolata iz rana (MRSA, E. coli, P. aeruginosa, Еnterococcus faecalis i Proteus mirabilis) bez
otpuštanja povidon-joda u okolinu (3). Isto tako, kompozitni Zn-alginatni hidrogelovi su otpuštali jone
cinka uz otpuštanje AU čestica sa adsorbovanim povidon-jodom što je prouzrokovalo dodatno
mikrobicidno dejstvo na jedan divlji soj gljivice Candida albicans. Dobijeni baktericidni efekti su
pripisani efikasnoj adsorpciji bakterija na čestice AU i daljem direktnom kontaktu adsorbovanog joda
sa ćelijskom membranom bakterija, dok je antifungalna aktivnost u odnosu na C. albicans pripisana
otpuštenim Zn 2+ jonima.
Može se zaključiti da su razvijeni kompozitni alginatni hdrogelovi pokazali veliki potencijal za
primenu u raznovrsnim multifunkcionalnim oblogama za rane prilagođenim specifičnim potrebama.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Multifunctional composites based on alginate hydrogels for potential use in wound dressings
T1  - Multifunkcionalni kompoziti na bazi alginatnih hidrogelova za potencijalnu primenu u oblogama za rane
VL  - 71
IS  - 5 suplement
SP  - S22
EP  - S23
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4666
ER  - 

@conference{
author = "Obradović, Bojana and Stojkovska, Jasmina and Osmokrović, Andrea and Mišković Stanković, Vesna and Jančić, Ivan and Milenković, Marina",
year = "2021",
abstract = "Alginate hydrogels are widely used in wound dressings due to hydrophilicity, biocompatibility,
flexibility, and high sorption capacity, providing effective moisture regulation in wounds and inducing
rapid granulation and reepithelization of the damaged tissue. However, these dressings are not
bioactive so that different methodologies have been investigated to extend functionality of alginate
hydrogels.
In the present work, we show several approaches to achieve this aim by addition of different
biologically active components. These include incorporation of silver nanoparticles as potent
antimicrobial agents (1), bioactive honey components (2), activated charcoal (AC) particles as carriers
of therapeutically active agents (3) as well as the use of Zn-alginate hydrogels that release zinc ions (4).
The obtained composites were comprehensively characterized regarding composition, cytotoxicity,
antibacterial activity, release kinetics of active agents and wound treatment in a rat model.
Ag/alginate nanocomposite hydrogels releasing silver ions and/or nanoparticles exhibited high
bactericidal activity against a broad spectrum of standard and multi-drug resistant clinical bacterial
strains (Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus – MRSA,
Acinetobacter baumannii and Pseudomonas aeruginosa). Especially interesting results were obtained
against 13 clinical isolates of A. baumannii, which were completely extinguished over 48 h in 6 cases
(2). However, in 3 clinical isolates, antibacterial effects were not noticed implying possibility for
development of bacterial resistance to silver. In the treatment of 2nd degree burns in rats Ag/alginate
nanocomposites exhibited the same efficiency as commercial medical products (5).
Composite alginate hydrogels with immobilized AC particles impregnated with povidone iodine
(PVP-I) as a model therapeutically active agent, were developed with the aim to provide controlled
particle release in the wound without actually releasing the adsorbed substance, thus achieving the
desired activity without adverse effects by systemic absorption. The composite Ca-alginate hydrogels
induced strong bactericidal effects against two standard bacterial strains and clinical multi-resistant
wound isolates (MRSA, E. coli, P. aeruginosa, Еnterococcus faecalis and Proteus mirabilis) without
releasing PVP-I in the environment (3). Furthermore, composite Zn-alginate hydrogels released zinc
ions in addition to AC particles with adsorbed PVP-I, which induced additional microbicidal effects on
one wild yeast strain (Candida albicans). The obtained bactericidal effects were ascribed to effective
adsorption of bacteria onto AC particles and further direct contact with the adsorbed iodine, while the
antifungal activity against C. albicans was assigned to released Zn 2+.
Overall, the developed composite alginate hydrogels have shown high potentials for utilization
in variety of multifunctional wound dressings according to the specific needs., Alginatni hidrogelovi se široko koriste u oblogama za rane zbog svoje hidrofilnosti,
biokompatibilnosti, fleksibilnosti i velikog sorpcionog kapaciteta čime obezbeđuju efikasnu regulaciju
vlažnosti rane i podstiču brzu granulaciju i reepitelizaciju oštećenog tkiva. Međutim, ove obloge nisu
bioaktivne tako da su istraživane različite metodologije kako bi se proširila funkcionalnost alginatnih
hidrogelova.
U ovom radu je prikazano nekoliko pristupa ostvarivanju tog cilja dodatkom različitih biološki
aktivnih komponenata. Ovi pristupi uključuju inkorporaciju nanočestica srebra kao potentnog
antimikrobnog agensa (1), bioaktivnih komponenata meda (2), čestica aktivnog uglja (AU) kao nosača
terapeutski aktivnih agenasa (3), kao i primenu hidrogelova Zn-alginata koji otpuštaju jone cinka.
Dobijeni kompoziti su sveobuhvatno karakterisani u pogledu sastava, citotoksičnosti, antibakterijske
aktivnosti, kinetike otpuštanja aktivnih agenasa i tretmana rana u eksperimentalnom modelu
opekotina na pacovima.
Ag/alginatni nanokompozitni hydrogelovi su usled otpuštanja jona i/ili nanočestica srebra,
pokazali izraženu baktericidnu aktivnost prema širokom spektru standardnih i kliničkih multi-
rezistentnih bakterijskih sojeva (Escherichia coli, Staphylococcus aureus, meticilin-resistentni
Staphylococcus aureus – MRSA, Acinetobacter baumannii i Pseudomonas aeruginosa). Posebno
interesantni rezultati su dobijeni u kulturama 13 kliničkih izolata A. baumannii, gde je u 6 slučajeva
postignut potpun baktericidan efekat u toku 48 h (2). Ipak, kod 3 klinička izolata nije postignuto
antibakterijsko dejstvo što ukazuje na mogućnost razvoja bakterijske rezistencije na srebro. U
tretmanu opekotina drugog stepena na pacovima, Ag/alginatni nanokompoziti su pokazali istu
efikasnost kao komercijalni medicinski proizvodi.
Kompozitni alginatni hidrogelovi sa imobilisanim česticama AU impregniranih povidon-jodom
kao model terapeutski aktivnom komponentom, su razvijeni sa ciljem da obezbede kontrolisano
otpuštanje čestica AU u rani bez otpuštanja adsorbovane supstance kako bi se na taj način postiglo
željeno dejstvo bez neželjenih efekata sistemske apsorpcije. Kompozitni Ca-alginatni hidrogelovi su
pokazali jake baktericidne efekte na dva standardna bakterijska soja i nekoliko kliničkih multi-
rezistentnih izolata iz rana (MRSA, E. coli, P. aeruginosa, Еnterococcus faecalis i Proteus mirabilis) bez
otpuštanja povidon-joda u okolinu (3). Isto tako, kompozitni Zn-alginatni hidrogelovi su otpuštali jone
cinka uz otpuštanje AU čestica sa adsorbovanim povidon-jodom što je prouzrokovalo dodatno
mikrobicidno dejstvo na jedan divlji soj gljivice Candida albicans. Dobijeni baktericidni efekti su
pripisani efikasnoj adsorpciji bakterija na čestice AU i daljem direktnom kontaktu adsorbovanog joda
sa ćelijskom membranom bakterija, dok je antifungalna aktivnost u odnosu na C. albicans pripisana
otpuštenim Zn 2+ jonima.
Može se zaključiti da su razvijeni kompozitni alginatni hdrogelovi pokazali veliki potencijal za
primenu u raznovrsnim multifunkcionalnim oblogama za rane prilagođenim specifičnim potrebama.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Multifunctional composites based on alginate hydrogels for potential use in wound dressings, Multifunkcionalni kompoziti na bazi alginatnih hidrogelova za potencijalnu primenu u oblogama za rane",
volume = "71",
number = "5 suplement",
pages = "S22-S23",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4666"
}

Obradović, B., Stojkovska, J., Osmokrović, A., Mišković Stanković, V., Jančić, I.,& Milenković, M.. (2021). Multifunctional composites based on alginate hydrogels for potential use in wound dressings. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 71(5 suplement), S22-S23.
https://hdl.handle.net/21.15107/rcub_farfar_4666

Obradović B, Stojkovska J, Osmokrović A, Mišković Stanković V, Jančić I, Milenković M. Multifunctional composites based on alginate hydrogels for potential use in wound dressings. in Arhiv za farmaciju. 2021;71(5 suplement):S22-S23.
https://hdl.handle.net/21.15107/rcub_farfar_4666 .

Obradović, Bojana, Stojkovska, Jasmina, Osmokrović, Andrea, Mišković Stanković, Vesna, Jančić, Ivan, Milenković, Marina, "Multifunctional composites based on alginate hydrogels for potential use in wound dressings" in Arhiv za farmaciju, 71, no. 5 suplement (2021):S22-S23,
https://hdl.handle.net/21.15107/rcub_farfar_4666 .

TY  - JOUR
AU  - Stojkovska, Jasmina
AU  - Đurđević, Željka
AU  - Jančić, Ivan
AU  - Bufan, Biljana
AU  - Milenković, Marina
AU  - Janković, Radmila
AU  - Mišković-Stanković, Vesna
AU  - Obradović, Bojana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3169
AB  - In the present study, possibilities for using novel nanocomposites based on alginate and silver nanoparticles for wound treatment were investigated in a second-degree thermal burn model in Wistar rats. Silver nanoparticles (AgNPs) were electrochemically synthesized in alginate solutions that were further utilized to obtain the Ag/alginate solution and microfibers for subsequent in vivo studies. Daily applications of the Ag/alginate colloid solution, containing AgNPs, alginate and ascorbic acid (G3), wet Ag/alginate microfibers containing AgNPs (G5) and dry Ag/alginate microfibers containing AgNPs (G6) were compared to treatments with a commercial cream containing silver sulfadiazine (G2) and a commercial Ca-alginate wound dressing containing silver ions (G4), as well as to the untreated controls (G1). Results of the in vivo study have shown faster healing in treated wounds, which completely healed on day 19 (G4, G5 and G6) and 21 (G2 and G3) after the thermal injury, while the period for complete reepitelization of untreated wounds (G1) was 25 days. The macroscopic analysis has shown that scabs fell off between day 10 and 12 after the thermal injury induction in treated groups, whereas between day 15 and 16 in the control group. These macroscopic findings were supported by the results of histopathological analyses, which have shown enhanced granulation and reepithelization, reduced inflammation and improved organization of the extracellular matrix in treated groups without adverse effects. Among the treated groups, dressings based on Ca-alginate (G4-G6) induced enhanced healing as compared to the other two groups (G2, G3), which could be attributed to additional stimuli of released Ca2+. The obtained results indicated potentials of novel nanocomposites based on alginate and AgNPs for therapeutic applications in wound treatments.
PB  - Sage Publications Ltd, London
T2  - Journal of Biomaterials Applications
T1  - Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments
VL  - 32
IS  - 9
SP  - 1197
EP  - 1211
DO  - 10.1177/0885328218759564
ER  - 

@article{
author = "Stojkovska, Jasmina and Đurđević, Željka and Jančić, Ivan and Bufan, Biljana and Milenković, Marina and Janković, Radmila and Mišković-Stanković, Vesna and Obradović, Bojana",
year = "2018",
abstract = "In the present study, possibilities for using novel nanocomposites based on alginate and silver nanoparticles for wound treatment were investigated in a second-degree thermal burn model in Wistar rats. Silver nanoparticles (AgNPs) were electrochemically synthesized in alginate solutions that were further utilized to obtain the Ag/alginate solution and microfibers for subsequent in vivo studies. Daily applications of the Ag/alginate colloid solution, containing AgNPs, alginate and ascorbic acid (G3), wet Ag/alginate microfibers containing AgNPs (G5) and dry Ag/alginate microfibers containing AgNPs (G6) were compared to treatments with a commercial cream containing silver sulfadiazine (G2) and a commercial Ca-alginate wound dressing containing silver ions (G4), as well as to the untreated controls (G1). Results of the in vivo study have shown faster healing in treated wounds, which completely healed on day 19 (G4, G5 and G6) and 21 (G2 and G3) after the thermal injury, while the period for complete reepitelization of untreated wounds (G1) was 25 days. The macroscopic analysis has shown that scabs fell off between day 10 and 12 after the thermal injury induction in treated groups, whereas between day 15 and 16 in the control group. These macroscopic findings were supported by the results of histopathological analyses, which have shown enhanced granulation and reepithelization, reduced inflammation and improved organization of the extracellular matrix in treated groups without adverse effects. Among the treated groups, dressings based on Ca-alginate (G4-G6) induced enhanced healing as compared to the other two groups (G2, G3), which could be attributed to additional stimuli of released Ca2+. The obtained results indicated potentials of novel nanocomposites based on alginate and AgNPs for therapeutic applications in wound treatments.",
publisher = "Sage Publications Ltd, London",
journal = "Journal of Biomaterials Applications",
title = "Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments",
volume = "32",
number = "9",
pages = "1197-1211",
doi = "10.1177/0885328218759564"
}

Stojkovska, J., Đurđević, Ž., Jančić, I., Bufan, B., Milenković, M., Janković, R., Mišković-Stanković, V.,& Obradović, B.. (2018). Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments. in Journal of Biomaterials Applications
Sage Publications Ltd, London., 32(9), 1197-1211.
https://doi.org/10.1177/0885328218759564

Stojkovska J, Đurđević Ž, Jančić I, Bufan B, Milenković M, Janković R, Mišković-Stanković V, Obradović B. Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments. in Journal of Biomaterials Applications. 2018;32(9):1197-1211.
doi:10.1177/0885328218759564 .

Stojkovska, Jasmina, Đurđević, Željka, Jančić, Ivan, Bufan, Biljana, Milenković, Marina, Janković, Radmila, Mišković-Stanković, Vesna, Obradović, Bojana, "Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments" in Journal of Biomaterials Applications, 32, no. 9 (2018):1197-1211,
https://doi.org/10.1177/0885328218759564 . .