Polyhydroxyalkanoate/Antifungal Polyene Formulations with Monomeric Hydroxyalkanoic Acids for Improved Antifungal Efficiency

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 (~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.

Towards potential antifungal agents: synthesis, supramolecular self-assembly and in vitro activity of azole mono-, sesqui- and diterpenoids

“…5 Polyenes are fungicidal preparations that exhibit a strongly pronounced effect against a wide range of yeasts and fungi. 6 Azole (imidazole) antifungal drugs are examples of fun-gistatic drugs that act by inhibiting the synthesis of fungal cell membranes. This increases the fluidity and permeability of fungal membranes and prevents growth and division of fungal cells.…”

Scaffolds in the microbial resistant era: Fabrication, materials, properties and tissue engineering applications

“…The derived composite materials showed good antimicrobial properties against the E. coli bacteria and P. pastoris yeast. AMB was also incorporated into PHA matrices combined with the antifungal agent nystatin at different concentrations [ 385 ]. The formulations, tested against different pathogenic fungi ( C. albicans species and C. parapsilosis ) as well as filamentous fungi, demonstrated a robust antifungal effect.…”

“…The scaffold showed effective antifungal behavior in an in vivo study (mouse model) as well as good biocompatibility [ 395 ], indicating a good potential for wound healing. Cytotoxicity studies were carried out on general-purpose antifungal scaffolds for tissue engineering using several cell lines such as MSCs [ 390 ], fibroblasts [ 360 , 393 ], human endothelial cells, human carcinoma cells [ 389 ] and human endothelial cells [ 394 ], although biocompatibility assays were not reported in several studies [ 384 , 385 , 387 , 388 , 391 , 396 , 398 ].…”

Advanced Vesicular Systems for Antifungal Drug Delivery

“…Nystatin is a polyene antifungal drug that shows outstanding action against a wide range of yeast and fungi. Also, amphotericin-B is a polyene antifungal drug that has antifungal activity against Candida species [7].…”