Polyhydroxyalkanoate/Antifungal Polyene Formulations with Monomeric Hydroxyalkanoic Acids for Improved Antifungal Efficiency
Marina Pekmezovic,
Melina Kalagasidis Krusic,
Ivana Malagurski,
Jelena Milovanovic,
Karolina Stępień,
Maciej Guzik,
Romina Charifou,
Ramesh Babu,
Kevin O’Connor,
Jasmina Nikodinovic-Runic
Affiliations
Marina Pekmezovic
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11221 Belgrade, Serbia
Melina Kalagasidis Krusic
Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, 11000 Belgrade, Serbia
Ivana Malagurski
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11221 Belgrade, Serbia
Jelena Milovanovic
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11221 Belgrade, Serbia
Karolina Stępień
Centre for Preclinical Research and Technology, Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland
Maciej Guzik
Jerzy Haber Institute of Catalysis and Surface Chemistry Polish Academy of Sciences, Niezapominajek 8, 30-239 Krakow, Poland
Romina Charifou
AMBER Centre, CRANN Institute, School of Chemistry, Trinity College Dublin, D2 Dublin, Ireland
Ramesh Babu
AMBER Centre, CRANN Institute, School of Chemistry, Trinity College Dublin, D2 Dublin, Ireland
Kevin O’Connor
BiOrbic Bioeconomy SFI Research Centre, University College Dublin, Belfield, D4 Dublin 4, Ireland
Jasmina Nikodinovic-Runic
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11221 Belgrade, Serbia
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 (~50 µm). 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.
