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  - https://dais.sanu.ac.rs/123456789/12954
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
SP  - 696
VL  - 14
IS  - 4
DO  - 10.3390/pharmaceutics14040696
UR  - https://hdl.handle.net/21.15107/rcub_dais_12954
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",
pages = "696",
volume = "14",
number = "4",
doi = "10.3390/pharmaceutics14040696",
url = "https://hdl.handle.net/21.15107/rcub_dais_12954"
}

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
https://hdl.handle.net/21.15107/rcub_dais_12954

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
https://hdl.handle.net/21.15107/rcub_dais_12954 .

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 .,
https://hdl.handle.net/21.15107/rcub_dais_12954 .