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.
Highlights
Polyhydroxyalkanoates (PHAs) as biodegradable and bio-based materials have gained much of interest lately in a view of the global plastic waste crisis [1,2,3]; they possess unique material properties to meet biomedical application-specific requirements [4,5,6]
amphotericin B (AmB) was more efficient against the range of tested fungi in comparison to Nys, with Minimum inhibitory concentrations (MICs) values 2–16-fold lower than Nys
Monomers showed moderate to poor activity against fungal isolates, with C10-OH being more active than C8–OH especially in the case of C. parapsilosis (Table 1)
Summary
Polyhydroxyalkanoates (PHAs) as biodegradable and bio-based materials have gained much of interest lately in a view of the global plastic waste crisis [1,2,3]; they possess unique material properties to meet biomedical application-specific requirements [4,5,6]. PHAs are family of natural bacterial biopolyesters composed of a wide variety of hydroxyalkanoates monomers giving them tunable mechanical properties from brittle rigid plastics to gummy elastomers [7]. The most common and investigated PHA is poly-3-hydroxybutyrate (PHB). Medium chain length PHAs (mcl-PHAs) are attracting interest due to unique properties and specific monomer composition [15,16,17]
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