Abstract:Opportunistic fungal infections are responsible for over 1.5 million deaths per year. This has created a need for highly effective antifungal medication to be as potent as possible. In this study, we improved the efficacy of a common over the counter (OTC) antifungal skin medication, miconazole, by encapsulating nano-molecules of the drug in cholesterol/sodium oleate nano-vesicles. These nano-vesicles were characterized to optimize their size, zeta potential, polydispersity index and encapsulation efficiency. … Show more
“…Fungal infection has become a significant event leading to over 1.5 million deaths annually worldwide (Deaguero et al 2020 ). To date, the most common fungal infections related to human mortality and morbidity are caused by Cryptococcus , Candida , and Aspergillus (Boral et al 2018 ).…”
The morbidity and mortality caused by invasive fungal infections are increasing across the globe due to developments in transplant surgery, the use of immunosuppressive agents, and the emergence of drug-resistant fungal strains, which has led to a challenge in terms of treatment due to the limitations of three classes of drugs. Hence, it is imperative to establish effective strategies to identify and design new antifungal drugs. Drug repurposing is a potential way of expanding the application of existing drugs. Recently, various existing drugs have been shown to be useful in the prevention and treatment of invasive fungi. In this review, we summarize the currently used antifungal agents. In addition, the most up-to-date information on the effectiveness of existing drugs with antifungal activity is discussed. Moreover, the antifungal mechanisms of existing drugs are highlighted. These data will provide valuable knowledge to stimulate further investigation and clinical application in this field.
Key points
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Conventional antifungal agents have limitations due to the occurrence of drug-resistant strains.
•
Non-antifungal drugs act as antifungal agents in various ways toward different targets.
•
Non-antifungal drugs with antifungal activity are demonstrated as effective antifungal strategies.
“…Fungal infection has become a significant event leading to over 1.5 million deaths annually worldwide (Deaguero et al 2020 ). To date, the most common fungal infections related to human mortality and morbidity are caused by Cryptococcus , Candida , and Aspergillus (Boral et al 2018 ).…”
The morbidity and mortality caused by invasive fungal infections are increasing across the globe due to developments in transplant surgery, the use of immunosuppressive agents, and the emergence of drug-resistant fungal strains, which has led to a challenge in terms of treatment due to the limitations of three classes of drugs. Hence, it is imperative to establish effective strategies to identify and design new antifungal drugs. Drug repurposing is a potential way of expanding the application of existing drugs. Recently, various existing drugs have been shown to be useful in the prevention and treatment of invasive fungi. In this review, we summarize the currently used antifungal agents. In addition, the most up-to-date information on the effectiveness of existing drugs with antifungal activity is discussed. Moreover, the antifungal mechanisms of existing drugs are highlighted. These data will provide valuable knowledge to stimulate further investigation and clinical application in this field.
Key points
•
Conventional antifungal agents have limitations due to the occurrence of drug-resistant strains.
•
Non-antifungal drugs act as antifungal agents in various ways toward different targets.
•
Non-antifungal drugs with antifungal activity are demonstrated as effective antifungal strategies.
“…11 .d to simulate permeation of the ATO-EMLs foam system concerning deep layers. Employed nanovesicles in topical therapy of fungus infection, enhance deep penetration resulting in promising clinical results ( Deaguero et al, 2020 ). Fig.…”
“…After 20 min of incubation with Hoechst, the cells were washed with 1× PBS 3 times, and 200 μL of fresh medium was added after removing the old medium. The fluorescence images were collected at 546 nm for Rhodamine B and 410 nm for Hoechst …”
Pathological fibrosis is distinguished from physiological wound healing by persistent myofibroblast activation, suggesting that therapies that induce myofibroblast apoptosis selectively could prevent progression and potentially reverse the established fibrosis, such as for scleroderma (a heterogeneous autoimmune disease characterized by multiorgan fibrosis). Navitoclax (NAVI) is a BCL-2/BCL-xL inhibitor with antifibrotic properties and has been investigated as a potential therapeutic for fibrosis. NAVI makes myofibroblasts particularly vulnerable to apoptosis. However, despite NAVI's significant potency, clinical translation of BCL-2 inhibitors, NAVI in this case, is hindered due to the risk of thrombocytopenia. Therefore, in this work, we utilized a newly developed ionic liquid formulation of NAVI for direct topical application to the skin, thereby avoiding systemic circulation and off-targetmediated side effects. The ionic liquid composed of choline and octanoic acid (COA) at a 1:2 molar ionic ratio increases skin diffusion and transportation of NAVI and maintains their retention within the dermis for a prolonged duration. Topical administration of NAVI-mediated BCL-xL and BCL-2 inhibition results in the transition of myofibroblast to fibroblast and ameliorates pre-existing fibrosis, as demonstrated in a scleroderma mouse model. We have observed a significant reduction of α-SMA and collagen, which are known as fibrosis marker proteins, as a result of the inhibition of antiapoptotic proteins BCL-2/BCL-xL. Overall, our findings show that COA-assisted topical delivery of NAVI upregulates apoptosis specific to myofibroblasts, with minimal presence of the drug in the systemic circulation, resulting in an accelerated therapeutic effect with no discernible drug-associated toxicity.
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