Polymeric Nanocapsules Containing Ozonated Oil and Terbinafine Hydrochloride as a Potential Treatment Against Dermatophytes.

Terbinafine hydrochloride is a synthetic allylamine whose mechanism of action consists of inhibiting the enzyme squalene epoxidase that participates in the first stage of ergosterol synthesis, interfering with fungal membrane function. Ozonated oils are used for topical application of ozone, producing reactive oxygen species that cause cellular damage in microorganisms, therefore being an alternative treatment for acute and chronic skin infections. This study aimed to develop and characterize Eudragit® RS100 nanocapsules, obtained by interfacial deposition of preformed polymer method, containing 0.5% terbinafine hydrochloride and 5% ozonated sunflower seed oil as a potential treatment against dermatophytes. The polymeric nanocapsules were characterized regarding particle size, zeta potential, pH, drug content, encapsulation efficiency, and stability. The in vitro drug release, in vitro skin permeation, and in vitro antifungal activity were also evaluated. The particle size was around 150 nm with a narrow size distribution, the zeta potential was around + 6 mV, and the pH was 2.2. The drug content was close to 95% with an encapsulation efficiency of 53%. The nanocapsules were capable to control the drug release and the skin permeation. The in vitro susceptibility test showed greater antifungal activity for the developed nanocapsules, against all dermatophyte strains tested, compared to the drug solution. Therefore, the polymeric nanocapsules suspension containing terbinafine hydrochloride and ozonated oil can be considered a potential high-efficacy candidate for the treatment of dermatophytosis, with a possible reduction in the drug dose and frequency of applications. Studies to evaluate safety and efficacy in vivo still need to be performed.

Fungicide Resistance in Fusarium graminearum Species Complex.

Fusariosis affects cereal grain crops worldwide and is responsible for devastating crops, reducing grain quality and yield, and producing strong mycotoxins. Benzimidazoles and triazoles were recommended to combat fusariosis; however, there were reports of resistance, making it necessary to reflect on the reasons for this occurrence. The purpose of this review was to evaluate the fusariosis resistance to the main agricultural fungicides, to observe whether this resistance can cause changes in the production of mycotoxins, and to verify the influence of resistance on the cereal grain production chain. Scientific articles were selected from the ScienceDirect, Scopus, and Pubmed databases, published at maximum 10 years ago and covering the main fungicide classes that combat phytopathogenesis and mycotoxin production. A high occurrence of resistance to carbendazim was found, while few reports of resistance to triazoles are available. The effectiveness of strobilurins is doubtful, due to an increase of mycotoxins linked to it. It is possible to conclude that the large-scale use of fungicides can select resistant strains that will contribute to an increase in the production of mycotoxins and harm sectors of the world economy, not only the agriculture, but also sanitation and foreign trade.

In silico and in vitro analysis of the mechanisms of action of nitroxoline against some medically important opportunistic fungi.

The increasing resistance to antifungal agents associated with toxicity and interactions turns therapeutic management of fungal infections difficult. This scenario emphasizes the importance of drug repositioning, such as nitroxoline - a urinary antibacterial agent that has shown potential antifungal activity. The aims of this study were to discover the possible therapeutic targets of nitroxoline using an in silico approach, and to determine the in vitro antifungal activity of the drug against the fungal cell wall and cytoplasmic membrane. We explored the biological activity of nitroxoline using PASS, SwissTargetPrediction and Cortellis Drug Discovery Intelligence web tools. After confirmation, the molecule was designed and optimized in HyperChem software. GOLD 2020.1 software was used to predict the interactions between the drug and the target proteins. In vitro investigation evaluated the effect of nitroxoline on the fungal cell wall through sorbitol protection assay. Ergosterol binding assay was carried out to assess the effect of the drug on the cytoplasmic membrane. In silico investigation revealed biological activity with alkane 1-monooxygenase and methionine aminopeptidase enzymes, showing nine and five interactions in the molecular docking, respectively. In vitro results exhibited no effect on the fungal cell wall or cytoplasmic membrane. Finally, nitroxoline has potential as an antifungal agent due to the interaction with alkane 1-monooxygenase and methionine aminopeptidase enzymes, which are not the main human therapeutic targets. These results have potentially revealed a new biological target for the treatment of fungal infections. We also consider that further studies are required to confirm the biological activity of nitroxoline on fungal cells, mainly the confirmation of the alkB gene.