TY  - JOUR
AU  - Pavić, Aleksandar
AU  - Stojanović, Zoran
AU  - Pekmezović, Marina
AU  - Veljović, Đorđe
AU  - O’connor, Kevin
AU  - Malagurski, Ivana
AU  - Nikodinović-Runić, Jasmina
PY  - 2022
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/5104
AB  - Immobilizing antifungal polyenes such as nystatin (Nys) and amphotericin B (AmB) into biodegradable formulations is advantageous compared to free drug administration providing sustained release, reduced dosing due to localized targeting and overall reduced systemic drug toxicity. In this study, we encapsulated Nys and AmB in medium chain length polyhydroxyalkanoates (mcl-PHA) microspheres (7–8 µm in diameter). The obtained formulations have been validated for antifungal activity in vitro against a panel of pathogenic fungi including species of Candida, Aspergillus, Microsporum and Trichophyton genera and toxicity and efficacy in vivo using the zebrafish model of disseminated candidiasis. While free polyenes, especially AmB, were highly toxic to zebrafish embryos at the effective (MIC) doses, after their loading into mcl-PHA microspheres, inner organ toxicity and teratogenicity associated with both drugs were not observed, even at 100 × MIC doses. The obtained mcl-PHA/polyene formulations have successfully eradicated C. albicans infection and showed an improved therapeutic profile in zebrafish by enhancing infected embryos survival. This approach is contributing to the antifungal arsenal as polyenes, although the first broad-spectrum antifungals on the market are still the gold standard for treatment of fungal infections.
PB  - MDPI
T2  - Pharmaceutics
T1  - Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model
IS  - 4
SP  - 696
VL  - 14
DO  - 10.3390/pharmaceutics14040696
ER  - 

@article{
author = "Pavić, Aleksandar and Stojanović, Zoran and Pekmezović, Marina and Veljović, Đorđe and O’connor, Kevin and Malagurski, Ivana and Nikodinović-Runić, Jasmina",
year = "2022",
abstract = "Immobilizing antifungal polyenes such as nystatin (Nys) and amphotericin B (AmB) into biodegradable formulations is advantageous compared to free drug administration providing sustained release, reduced dosing due to localized targeting and overall reduced systemic drug toxicity. In this study, we encapsulated Nys and AmB in medium chain length polyhydroxyalkanoates (mcl-PHA) microspheres (7–8 µm in diameter). The obtained formulations have been validated for antifungal activity in vitro against a panel of pathogenic fungi including species of Candida, Aspergillus, Microsporum and Trichophyton genera and toxicity and efficacy in vivo using the zebrafish model of disseminated candidiasis. While free polyenes, especially AmB, were highly toxic to zebrafish embryos at the effective (MIC) doses, after their loading into mcl-PHA microspheres, inner organ toxicity and teratogenicity associated with both drugs were not observed, even at 100 × MIC doses. The obtained mcl-PHA/polyene formulations have successfully eradicated C. albicans infection and showed an improved therapeutic profile in zebrafish by enhancing infected embryos survival. This approach is contributing to the antifungal arsenal as polyenes, although the first broad-spectrum antifungals on the market are still the gold standard for treatment of fungal infections.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model",
number = "4",
pages = "696",
volume = "14",
doi = "10.3390/pharmaceutics14040696"
}

Pavić, A., Stojanović, Z., Pekmezović, M., Veljović, Đ., O’connor, K., Malagurski, I.,& Nikodinović-Runić, J.. (2022). Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model. in Pharmaceutics
MDPI., 14(4), 696.
https://doi.org/10.3390/pharmaceutics14040696

Pavić A, Stojanović Z, Pekmezović M, Veljović Đ, O’connor K, Malagurski I, Nikodinović-Runić J. Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model. in Pharmaceutics. 2022;14(4):696.
doi:10.3390/pharmaceutics14040696 .

Pavić, Aleksandar, Stojanović, Zoran, Pekmezović, Marina, Veljović, Đorđe, O’connor, Kevin, Malagurski, Ivana, Nikodinović-Runić, Jasmina, "Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model" in Pharmaceutics, 14, no. 4 (2022):696,
https://doi.org/10.3390/pharmaceutics14040696 . .

TY  - JOUR
AU  - Pekmezović, Marina
AU  - Kalagasidis Krušić, Melina
AU  - Malagurski, Ivana
AU  - Milovanović, Jelena
AU  - Stepien, Karolina
AU  - Guzik, Maciej
AU  - Charifou, Romina
AU  - Babu, Ramesh
AU  - O'Connor, Kevin
AU  - Nikodinović-Runić, Jasmina
PY  - 2021
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4826
AB  - Novel biodegradable and biocompatible formulations of "old" but "gold" drugs such as nystatin (Nys) and amphotericin B (AmB) were made using a biopolymer as a matrix. Medium chain length polyhydroxyalkanoates (mcl-PHA) were used to formulate both polyenes (Nys and AmB) in the form of films (similar to 50 mu m). Thermal properties and stability of the materials were not significantly altered by the incorporation of polyenes in mcl-PHA, but polyene containing materials were more hydrophobic. These formulations were tested in vitro against a panel of pathogenic fungi and for antibiofilm properties. The films containing 0.1 to 2 weight % polyenes showed good activity and sustained polyene release for up to 4 days. A PHA monomer, namely 3-hydroxydecanoic acid (C10-OH), was added to the films to achieve an enhanced synergistic effect with polyenes against fungal growth. Mcl-PHA based polyene formulations showed excellent growth inhibitory activity against both Candida yeasts (C. albicans ATCC 1023, C. albicans SC5314 (ATCC MYA-2876), C. parapsilosis ATCC 22019) and filamentous fungi (Aspergillus fumigatus ATCC 13073; Trichophyton mentagrophytes ATCC 9533, Microsporum gypseum ATCC 24102). All antifungal PHA film preparations prevented the formation of a C. albicans biofilm, while they were not efficient in eradication of mature biofilms, rendering them suitable for the transdermal application or as coatings of implants.
T2  - Antibiotics
T1  - Polyhydroxyalkanoate/Antifungal Polyene Formulations with Monomeric Hydroxyalkanoic Acids for Improved Antifungal Efficiency
IS  - 6
SP  - 737
VL  - 10
DO  - 10.3390/antibiotics10060737
ER  - 

@article{
author = "Pekmezović, Marina and Kalagasidis Krušić, Melina and Malagurski, Ivana and Milovanović, Jelena and Stepien, Karolina and Guzik, Maciej and Charifou, Romina and Babu, Ramesh and O'Connor, Kevin and Nikodinović-Runić, Jasmina",
year = "2021",
abstract = "Novel biodegradable and biocompatible formulations of "old" but "gold" drugs such as nystatin (Nys) and amphotericin B (AmB) were made using a biopolymer as a matrix. Medium chain length polyhydroxyalkanoates (mcl-PHA) were used to formulate both polyenes (Nys and AmB) in the form of films (similar to 50 mu m). Thermal properties and stability of the materials were not significantly altered by the incorporation of polyenes in mcl-PHA, but polyene containing materials were more hydrophobic. These formulations were tested in vitro against a panel of pathogenic fungi and for antibiofilm properties. The films containing 0.1 to 2 weight % polyenes showed good activity and sustained polyene release for up to 4 days. A PHA monomer, namely 3-hydroxydecanoic acid (C10-OH), was added to the films to achieve an enhanced synergistic effect with polyenes against fungal growth. Mcl-PHA based polyene formulations showed excellent growth inhibitory activity against both Candida yeasts (C. albicans ATCC 1023, C. albicans SC5314 (ATCC MYA-2876), C. parapsilosis ATCC 22019) and filamentous fungi (Aspergillus fumigatus ATCC 13073; Trichophyton mentagrophytes ATCC 9533, Microsporum gypseum ATCC 24102). All antifungal PHA film preparations prevented the formation of a C. albicans biofilm, while they were not efficient in eradication of mature biofilms, rendering them suitable for the transdermal application or as coatings of implants.",
journal = "Antibiotics",
title = "Polyhydroxyalkanoate/Antifungal Polyene Formulations with Monomeric Hydroxyalkanoic Acids for Improved Antifungal Efficiency",
number = "6",
pages = "737",
volume = "10",
doi = "10.3390/antibiotics10060737"
}

Pekmezović, M., Kalagasidis Krušić, M., Malagurski, I., Milovanović, J., Stepien, K., Guzik, M., Charifou, R., Babu, R., O'Connor, K.,& Nikodinović-Runić, J.. (2021). Polyhydroxyalkanoate/Antifungal Polyene Formulations with Monomeric Hydroxyalkanoic Acids for Improved Antifungal Efficiency. in Antibiotics, 10(6), 737.
https://doi.org/10.3390/antibiotics10060737

Pekmezović M, Kalagasidis Krušić M, Malagurski I, Milovanović J, Stepien K, Guzik M, Charifou R, Babu R, O'Connor K, Nikodinović-Runić J. Polyhydroxyalkanoate/Antifungal Polyene Formulations with Monomeric Hydroxyalkanoic Acids for Improved Antifungal Efficiency. in Antibiotics. 2021;10(6):737.
doi:10.3390/antibiotics10060737 .

Pekmezović, Marina, Kalagasidis Krušić, Melina, Malagurski, Ivana, Milovanović, Jelena, Stepien, Karolina, Guzik, Maciej, Charifou, Romina, Babu, Ramesh, O'Connor, Kevin, Nikodinović-Runić, Jasmina, "Polyhydroxyalkanoate/Antifungal Polyene Formulations with Monomeric Hydroxyalkanoic Acids for Improved Antifungal Efficiency" in Antibiotics, 10, no. 6 (2021):737,
https://doi.org/10.3390/antibiotics10060737 . .

TY  - JOUR
AU  - Mandić, Mina
AU  - Spasić, Jelena
AU  - Ponjavić, Marijana
AU  - Nikolić, Marija
AU  - Ćosović, Vladan
AU  - O'Connor, Kevin E.
AU  - Nikodinović-Runić, Jasmina
AU  - Đokić, Lidija
AU  - Jeremić, Sanja
PY  - 2019
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4250
AB  - Petrochemical plastics are generally recalcitrant to microbial degradation and accumulate in the environment. Biodegradable polymers obtained synthetically like poly(epsilon-caprolactone) (PCL) or poly-hydroxyalkanoates (PHA), obtained biotechnologically, have shown great potential as a replacement for petroleum-based plastics. Nevertheless, their biodegradation and environmental faith have been less examined. In this study, thin films of PCL (200 mu m) and medium chain length PHA (mcl-PHA, 70 M fraction of 3-hydroxyoctanoate and 30 M fraction of 3-hydroxydecanoate, 600 mu m) were exposed to total protein preparations (extracellular proteins combined with a crude cell extract) of soil isolates Pseudomonas chiororaphis B-561 and Streptomyces sp. BV315 that had been grown on waste cooking oil as a sole carbon source. Biodegradation potential of two polyesters was evaluated in buffer with total protein preparations and in a laboratory compost model system augmented with selected bacteria. Overall, PCL showed better biodegradation properties in comparison to mcl-PHA. Both materials showed surface erosion after 4-weeks of exposure to total protein preparations of both strains, with a moderate weight loss of 1.3% when P. chlororaphis13-561 was utilized. In laboratory compost model system PCL and mcl-PHA showed significant weight loss ranging from 13 to 17% when Streptomyces sp. BV315 culture was used. Similar weight loss of PCL and mcl-PHA was achieved for 4 and 8 weeks, respectively indicating slower degradation of mcl-PHA. Growth on waste cooking oil as a sole carbon source increased the potential of both tested strains to degrade PCL and mcl-PHA, making them good candidates for augmentation of compost cultures in waste management of both waste cooking oils and biodegradable polymers.
PB  - Elsevier Sci Ltd, Oxford
T2  - Polymer Degradation and Stability
T1  - Biodegradation of poly(epsilon-caprolactone) (PCL) and medium chain length polyhydroxyalkanoate (mcl-PHA) using whole cells and cell free protein preparations of Pseudomonas and Streptomyces strains grown on waste cooking oil
EP  - 168
SP  - 160
VL  - 162
DO  - 10.1016/j.polymdegradstab.2019.02.012
ER  - 

@article{
author = "Mandić, Mina and Spasić, Jelena and Ponjavić, Marijana and Nikolić, Marija and Ćosović, Vladan and O'Connor, Kevin E. and Nikodinović-Runić, Jasmina and Đokić, Lidija and Jeremić, Sanja",
year = "2019",
abstract = "Petrochemical plastics are generally recalcitrant to microbial degradation and accumulate in the environment. Biodegradable polymers obtained synthetically like poly(epsilon-caprolactone) (PCL) or poly-hydroxyalkanoates (PHA), obtained biotechnologically, have shown great potential as a replacement for petroleum-based plastics. Nevertheless, their biodegradation and environmental faith have been less examined. In this study, thin films of PCL (200 mu m) and medium chain length PHA (mcl-PHA, 70 M fraction of 3-hydroxyoctanoate and 30 M fraction of 3-hydroxydecanoate, 600 mu m) were exposed to total protein preparations (extracellular proteins combined with a crude cell extract) of soil isolates Pseudomonas chiororaphis B-561 and Streptomyces sp. BV315 that had been grown on waste cooking oil as a sole carbon source. Biodegradation potential of two polyesters was evaluated in buffer with total protein preparations and in a laboratory compost model system augmented with selected bacteria. Overall, PCL showed better biodegradation properties in comparison to mcl-PHA. Both materials showed surface erosion after 4-weeks of exposure to total protein preparations of both strains, with a moderate weight loss of 1.3% when P. chlororaphis13-561 was utilized. In laboratory compost model system PCL and mcl-PHA showed significant weight loss ranging from 13 to 17% when Streptomyces sp. BV315 culture was used. Similar weight loss of PCL and mcl-PHA was achieved for 4 and 8 weeks, respectively indicating slower degradation of mcl-PHA. Growth on waste cooking oil as a sole carbon source increased the potential of both tested strains to degrade PCL and mcl-PHA, making them good candidates for augmentation of compost cultures in waste management of both waste cooking oils and biodegradable polymers.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Polymer Degradation and Stability",
title = "Biodegradation of poly(epsilon-caprolactone) (PCL) and medium chain length polyhydroxyalkanoate (mcl-PHA) using whole cells and cell free protein preparations of Pseudomonas and Streptomyces strains grown on waste cooking oil",
pages = "168-160",
volume = "162",
doi = "10.1016/j.polymdegradstab.2019.02.012"
}

Mandić, M., Spasić, J., Ponjavić, M., Nikolić, M., Ćosović, V., O'Connor, K. E., Nikodinović-Runić, J., Đokić, L.,& Jeremić, S.. (2019). Biodegradation of poly(epsilon-caprolactone) (PCL) and medium chain length polyhydroxyalkanoate (mcl-PHA) using whole cells and cell free protein preparations of Pseudomonas and Streptomyces strains grown on waste cooking oil. in Polymer Degradation and Stability
Elsevier Sci Ltd, Oxford., 162, 160-168.
https://doi.org/10.1016/j.polymdegradstab.2019.02.012

Mandić M, Spasić J, Ponjavić M, Nikolić M, Ćosović V, O'Connor KE, Nikodinović-Runić J, Đokić L, Jeremić S. Biodegradation of poly(epsilon-caprolactone) (PCL) and medium chain length polyhydroxyalkanoate (mcl-PHA) using whole cells and cell free protein preparations of Pseudomonas and Streptomyces strains grown on waste cooking oil. in Polymer Degradation and Stability. 2019;162:160-168.
doi:10.1016/j.polymdegradstab.2019.02.012 .

Mandić, Mina, Spasić, Jelena, Ponjavić, Marijana, Nikolić, Marija, Ćosović, Vladan, O'Connor, Kevin E., Nikodinović-Runić, Jasmina, Đokić, Lidija, Jeremić, Sanja, "Biodegradation of poly(epsilon-caprolactone) (PCL) and medium chain length polyhydroxyalkanoate (mcl-PHA) using whole cells and cell free protein preparations of Pseudomonas and Streptomyces strains grown on waste cooking oil" in Polymer Degradation and Stability, 162 (2019):160-168,
https://doi.org/10.1016/j.polymdegradstab.2019.02.012 . .