scholarly journals Nanoarchitectures in Management of Fungal Diseases: An Overview

2021 ◽  
Vol 11 (15) ◽  
pp. 7119
Author(s):  
Vijay Mishra ◽  
Manvendra Singh ◽  
Yachana Mishra ◽  
Nitin Charbe ◽  
Pallavi Nayak ◽  
...  

Fungal infections, from mild itching to fatal infections, lead to chronic diseases and death. Antifungal agents have incorporated chemical compounds and natural products/phytoconstituents in the management of fungal diseases. In contrast to antibacterial research, novel antifungal drugs have progressed more swiftly because of their mild existence and negligible resistance of infections to antifungal bioactivities. Nanotechnology-based carriers have gained much attention due to their magnificent abilities. Nanoarchitectures have served as excellent carriers/drug delivery systems (DDS) for delivering antifungal drugs with improved antifungal activities, bioavailability, targeted action, and reduced cytotoxicity. This review outlines the different fungal diseases and their treatment strategies involving various nanocarrier-based techniques such as liposomes, transfersomes, ethosomes, transethosomes, niosomes, spanlastics, dendrimers, polymeric nanoparticles, polymer nanocomposites, metallic nanoparticles, carbon nanomaterials, and nanoemulsions, among other nanotechnological approaches.

2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.


2021 ◽  
Author(s):  
Mariolina Bruno ◽  
Vasiliki Matzaraki ◽  
Frank L van de Veerdonk ◽  
Vinod Kumar ◽  
Mihai G. Netea

Infectious diseases are a leading cause of morbidity and mortality worldwide and human pathogens have long been recognized as one of the main sources of evolutionary pressure, resulting in a high variable genetic background in immune-related genes. The study of the genetic contribution to infectious diseases has undergone tremendous advances over the last decades. Here, focusing on genetic predisposition to fungal diseases, we provide an overview of the available approaches for studying human genetic susceptibility to infections, reviewing current methodological and practical limitations. We describe how the classical methods available, such as family-based studies and candidate-gene studies, have contributed to the discovery of crucial susceptibility factors for fungal infections. We will also discuss the contribution of novel unbiased approaches to the field, highlighting their success but also their limitations for the fungal immunology field. Finally, we show how a systems genomics approach can overcome those limitations and can lead to efficient prioritization and identification of genes and pathways with a critical role in susceptibility to fungal diseases. This knowledge will help stratify patients at risk groups and, subsequently, develop early appropriate prophylactic and treatment strategies.


2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Cristina Lazzarini ◽  
Krupanandan Haranahalli ◽  
Robert Rieger ◽  
Hari Krishna Ananthula ◽  
Pankaj B. Desai ◽  
...  

ABSTRACTThe incidence of invasive fungal infections has risen dramatically in recent decades. Current antifungal drugs are either toxic, likely to interact with other drugs, have a narrow spectrum of activity, or induce fungal resistance. Hence, there is a great need for new antifungals, possibly with novel mechanisms of action. Previously our group reported an acylhydrazone called BHBM that targeted the sphingolipid pathway and showed strong antifungal activity against several fungi. In this study, we screened 19 derivatives of BHBM. Three out of 19 derivatives were highly active againstCryptococcus neoformansin vitroand had low toxicity in mammalian cells. In particular, one of them, called D13, had a high selectivity index and showed better activity in an animal model of cryptococcosis, candidiasis, and pulmonary aspergillosis. D13 also displayed suitable pharmacokinetic properties and was able to pass through the blood-brain barrier. These results suggest that acylhydrazones are promising molecules for the research and development of new antifungal agents.


Author(s):  
Lisa Kirchhoff ◽  
Silke Dittmer ◽  
Ann-Kathrin Weisner ◽  
Jan Buer ◽  
Peter-Michael Rath ◽  
...  

Abstract Objectives Patients with immunodeficiency or cystic fibrosis frequently suffer from respiratory fungal infections. In particular, biofilm-associated fungi cause refractory infection manifestations, linked to increased resistance to anti-infective agents. One emerging filamentous fungus is Lomentospora prolificans. Here, the biofilm-formation capabilities of L. prolificans isolates were investigated and the susceptibility of biofilms to various antifungal agents was analysed. Methods Biofilm formation of L. prolificans (n = 11) was estimated by crystal violet stain and antibiofilm activity was additionally determined via detection of metabolically active biofilm using an XTT assay. Amphotericin B, micafungin, voriconazole and olorofim were compared with regard to their antibiofilm effects when added prior to adhesion, after adhesion and on mature and preformed fungal biofilms. Imaging via confocal laser scanning microscopy was carried out to demonstrate the effect of drug treatment on the fungal biofilm. Results Antibiofilm activities of the tested antifungal agents were shown to be most effective on adherent cells whilst mature biofilm was the most resistant. The most promising antibiofilm effects were detected with voriconazole and olorofim. Olorofim showed an average minimum biofilm eradication concentration (MBEC) of 0.06 mg/L, when added prior to and after adhesion. The MBECs of voriconazole were ≤4 mg/L. On mature biofilm the MBECs of olorofim and voriconazole were higher than the previously determined MICs against planktonic cultures. In contrast, amphotericin B and especially micafungin did not exhibit sufficient antibiofilm activity against L. prolificans. Conclusions To our knowledge, this is the first study demonstrating the antibiofilm potential of olorofim against the human pathogenic fungus L. prolificans.


2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Juliana Alves Parente-Rocha ◽  
Alexandre Melo Bailão ◽  
André Correa Amaral ◽  
Carlos Pelleschi Taborda ◽  
Juliano Domiraci Paccez ◽  
...  

Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs.


2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Claudia Spampinato ◽  
Darío Leonardi

The genusCandidaincludes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised.Candidainfections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genusCandidaand yeast infection causes and then focus on current antifungal drugs and resistance mechanisms. An overview of new therapeutic alternatives for the treatment ofCandidainfections is also provided.


Author(s):  
Todd Patrick McCarty ◽  
Peter G. Pappas

In many ways, fungal diseases are forgotten or neglected. Given the significantly lower frequency compared to similar bacterial etiologies across the spectrum of infectious syndromes, it makes sense that anti-bacterial agents have seen the bulk of development in recent decades. The vast majority of new antifungal medications approved for use in the past 10 years have been new versions in the same class as existing agents. Clinical mycology is crying out for new mechanisms of action in the setting of rising resistance and emergence of new organisms. Fortunately, this trend appears to be reversing. There are numerous agents in advanced stages of development offering novel dosing regimens and mechanisms of action to combat these threats. Herein we review seven antifungal agents that we hope to see come to market in the coming years to aid physicians in the treatment of mucocutaneous and invasive fungal infections.


2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Gina Wall ◽  
Jose L. Lopez-Ribot

ABSTRACT Fungal organisms are ubiquitous in nature, and progress of modern medicine is creating an expanding number of severely compromised patients susceptible to a variety of opportunistic fungal infections. These infections are difficult to diagnose and treat, leading to high mortality rates. The limited antifungal arsenal, the toxicity of current antifungal drugs, the development of resistance, and the emergence of new multidrug-resistant fungi, all highlight the urgent need for new antifungal agents. Unfortunately, the development of a novel antifungal is a rather long and expensive proposition, and no new classes of antifungal agents have reached the market in the last 2 decades. Drug repurposing, or finding new indications for old drugs, represents a promising alternative pathway to drug development that is particularly appealing within the academic environment. In the last few years, there has been a growing interest in repurposing approaches in the antifungal arena, with multiple groups of investigators having performed screenings of different repurposing libraries against different pathogenic fungi in search for drugs with previously unrecognized antifungal effects. Overall, these repurposing efforts may lead to the fast deployment of drugs with novel antifungal activity, which can rapidly bring benefits to patients, while at the same time reducing health care costs.


Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1480 ◽  
Author(s):  
Iwona Gabriel

Frequent fungal infections in immunocompromised patients and mortality due to invasive mycosis are important clinical problems. Opportunistic pathogenic Candida species remain one of the leading causes of systemic mycosis worldwide. The repertoire of antifungal chemotherapeutic agents is very limited. Although new antifungal drugs such as lanosterol 14α-demethylase and β-glucan synthase inhibitors have been introduced into clinical practice, the development of multidrug resistance has become increasingly significant. The urgency to expand the range of therapeutic options for the treatment of fungal infections has led researchers in recent decades to seek alternative antifungal targets to the conventional ones currently used. Among them, many compounds containing an acridine scaffold have been synthesized and tested. In this review, the applicability of acridines and their functional analogues acridones as antifungal agents is described. Acridine derivatives usage in photoantifungal chemotherapy, interactions with fungal transporters resulting in modulation of efflux/influx pumps and the effect of acridine derivatives on fungal topoisomerases are discussed. This article explores new perspectives on the mechanisms of antifungal acridine-peptide conjugates and acridine-based hybrid molecules to effectively combat fungal infections.


Author(s):  
Alexander Yu. Maksimov ◽  
Svetlana Yu. Balandina ◽  
Pavel A. Topanov ◽  
Irina V. Mashevskaya ◽  
Sandeep Chaudhary

: In recent decades, there has been a significant increase in the number of fungal diseases. This is due to a wide spectrum of action, immunosuppressants and other group drugs. In terms of frequency, rapid spread and globality, fungal infections are approaching acute respiratory infections. Antimycotics are medicinal substances endorsed with fungicidal or fungistatic properties. For the treatment of fungal diseases, several groups of compounds are used that differ in their origin (natural or synthetic), molecular targets and mechanism of action, antifungal effect (fungicidal or fungistatic), indications for use (local or systemic infections), methods of administration (parenteral, oral, outdoor). Several efforts have been made by various medicinal chemists around the world for the development of antifungal drugs with high efficacy with least toxicity and maximum selectivity in the area of antifungal chemotherapy. The pharmacokinetic properties of the new antimycotics are also important: the ability to penetrate biological barriers, be absorbed and distributed in tissues and organs, get accumulated in tissues affected by micromycetes, drug metabolism in the intestinal microflora and human organs, and in the kinetics of excretion from the body. There are several ways to search for new effective antimycotics: - Obtaining new derivatives of the already used classes of antimycotics with improved activity properties. - Screening of new chemical classes of synthetic antimycotic compounds. - Screening of natural compounds. - Identification of new unique molecular targets in the fungal cell. - Development of new compositions and dosage forms with effective delivery vehicles. The methods of informatics, bioinformatics, genomics and proteomics were extensively investigated for the development of new antimycotics. These techniques were employed in finding and identification of new molecular proteins in a fungal cell; in the determination of the selectivity of drug-protein interactions, evaluation of drug-drug interactions and synergism of drugs; determination of the structure-activity relationship (SAR) studies; determination of the molecular design of the most active, selective and safer drugs for the humans, animals and plants. In medical applications, the methods of information analysis and pharmacogenomics allows to take into account the individual phenotype of the patient, the level of expression of the targets of antifungal drugs when choosing antifungal agents and its dosage. This review article incorporates some of the most significant studies covering the basic structures and approaches for the synthesis of antifungal drugs and the directions for their further development.


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