The Use of Nanoparticles as Effective and Versatile Antifungal Nanosystems Against a Wide Range of Fungal Species will Help us Defeat Fungal Infectious Diseases

Milad Talaiekhozani^*
*Correspondence: Milad Talaiekhozani, Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran, Email:

Introduction

From a medical standpoint, it is widely acknowledged that fungi play an important role in human infections. Infectious fungi, which previously had no effect on humans, are now included on the list of pathogenic organisms, which is expanding at an alarming rate. These fungi have emerged as one of the most frequent causes of mortality in this patient population due to their ability to adapt to a wide range of environmental conditions, which makes them a threat to the survival of immunocompromised patients. Because of this, it is crucial to correctly diagnose and treat infections of this kind, which calls for thorough knowledge in this area. Recent research show that more than 300 million people globally are infected by potentially lethal fungal infections, which result in about 1.4 million mortality annually. The creation of novel antifungals and the widespread use of these drugs over the past 20 years have dramatically changed how fungal infectious illnesses are managed. On the other hand, though, rising rates of drug resistance around the globe have masked such achievements.

Antiretroviral therapy (ART), which has been applied in industrialised countries, has directly contributed to a noticeable decrease in the occurrence of fungal infections among people with human immunodeficiency virus (HIV). Additionally, there has been a noticeable increase in the prevalence of fungal infections in developing countries where such drugs are not easily accessible. Additionally, the Use of invasive therapeutic interventions in healthcare settings, the use of immunosuppressive drugs after organ transplantation, the treatment of malignancies, the growing use of amphotericin B during empiric treatment, and the need for antifungal prophylaxis with azole derivatives have all contributed to significant shifts in the occurrence of various types of fungal infections with different patterns and, in particular, the emergence of drug resistance. Because of this, researchers have worked tirelessly to develop strategies that would limit drug resistance and negative side effects.

Description

Infection with fungi and development of biofilms

Several researchers have concentrated their efforts on the process of bacteria creating biofilms in recent years. This type of proliferation predominates in nature in comparison to free planktonic or cellular growth. However, it poses a concern, especially in clinical settings, due to its higher susceptibility to environmental factors and antimicrobial medications. Due to the characteristics of the environment, this is the case. Many species of yeast, filamentous, and dimorphic fungus have been classified as being able to multiply into colonies, and there has been an increase in interest in the biofilms that are created when pathogenic fungi are allowed to flourish. Sessile microbial populations make up biofilms, which are permanently attached to substrates or surfaces as well as to one another. They are protected by an extracellular matrix made primarily of polysaccharides and with a polymeric base. In compared to planktonic or free cells, these cells have a stronger resilience to therapy and a unique phenotype; they are also connected to the persistence of infections. Inorganic surfaces, such as those on catheters and prosthetics, can also serve as a surface for infectious fungus to adhere to In this situation, yeasts in particular are well-positioned to seize control and gain entry to the patient's circulatory system and, eventually, their interior tissues.

Given the substantial mortality risk linked with the spread of fungi, this is cause for alarm. Numerous diverse species have shown the ability to develop these populations, and the number of studies focusing on fungi biofilms has significantly increased. Paracoccidioides brasiliensis is a dimorphic fungus that causes paracoccidioidomycosis, a systemic fungal illness. Latin America is the original home of this illness. The biofilms that were created by this fungus while it was in the yeast phase were described by Sardi and colleagues in their work. They found that in vitro community growth was associated with decreased expression of phospholipase and increased expression of genes for adhesion molecules such as glyceraldehyde 3-phosphate dehydrogenase (GAPDH), enolase, aspartyl proteinase, and glycoprotein gp43. Dermatophytosis is one of the most common dermatomycoses observed in humans and other animals, and it is caused by fungi called dermatophyte. Onychomycosis is a type of dermatophytosis that regularly recurs and calls for prolonged, frequently ineffective treatment. Costa-Orlandi, et al. demonstrated in vitro biofilm development by two of the most widespread species found all over the world, namely Trichophyton mentagrophytes and T. rubrum, in light of this background and the theory of Burkhart, et al. which claims that biofilm development by dermatophytes may characterise dermatophytomas.

Application of antifungal nanomaterials for prevention and treatment

It is generally recognised that in some circumstances, nanoparticles can function as potent antifungal agents. Numerous investigations into the antifungal potential of nanostructures have been carried out, and the findings indicate that these nanoparticles have a significant suppressive effect on the vegetative growth of fungal mycelia. For instance, the potential antifungal activity of gold nanoparticles in Candida albicans biofilms has been studied. This is because Au nanoparticles have the capacity to increase the efficacy of photodynamic therapy when paired with a photosensitizer. Au nanoparticles have the ability to damage the pathogens' cellular membranes by coming into touch with the lipids and proteins of the pathogen. Additionally, the incorporation of metal nanoparticles and photosensitizers may reduce the likelihood of infections. is going to develop resistance to the effects of photodynamic therapy. Ag nanoparticles and propolis extract (PE) were tested for their efficacy against Candida species and other fungus mature biofilms by Kischkel, et al.

They found that the concentration required for the formulation to have fungicidal action was lower than the concentration required for cytotoxic action. High quantities of antifungal activity can be discovered in the nanostructures of noble metals like gold and silver. Nasar studied Aspergillus niger, a typical fungal pathogen, as well as the broad-spectrum antibacterial efficacy of Ag nanoparticles against pathogenic bacterial strains (Bacillus subtilis, Escherichia coli, and Klebsiella pneumonia). Ag nanoparticles have been shown to be effective antifungals in the management of cutaneous infectious disorders. Ag nanoparticles can also be used to get rid of Trichophyton mentagrophytes, Candida albicans, and Staphylococcus aureus, which are the most frequent causes of oral microbial infections in people. At extremely low concentrations (less than 100 ppm), the Ag nanoparticles were able to stop the growth of Fusarium oxysporum, which resulting in a decrease in mycotoxin production. Additionally, against Candida albicans, Fusarium oxysporum, and Microsporum canis, Kischkel, et al. demonstrated the antifungal ability of the Ag nanoparticles.

A study was conducted to better understand the cellular and molecular mechanisms of harmful effects brought on by Ag nanoparticles in Candida albicans, a common fungal pathogen. The effects of Ag nanoparticles on molecular and cellular targets were assessed using changes in surface topography, cellular ultrastructure, membrane microenvironment, membrane fluidity, membrane ergosterol, and fatty acids after monitoring the intracellular generation of ROS in the absence and presence of natural antioxidants. Spherical Ag nanoparticles (10–30 nm) showed a modest amount of inhibition at a concentration of 40 g/mL. This is the level of concentration necessary to prevent the growth of at least 90% of all organisms. Our research showed that Ag nanoparticles generated intracellular ROS in a dose-dependent manner that had antifungal properties. However, antioxidants that scavenge ROS were unable to protect against the mortality brought on by Ag nanoparticles. Following treatment with Ag nanoparticles, the membrane microenvironment, cellular ultrastructure, and surface morphology were all examined. Changes were seen in fatty acid content, ergosterol concentration, and membrane fluidity. In particular, oleic acid was impacted. Numerous cellular targets in the fungal cells were impacted by the Ag nanoparticles, all of which were necessary for drug resistance and pathogenicity. Additional biological targets for Ag nanoparticles were discovered by the research, some of which include fatty acids like oleic acid, which are necessary for the development of hyphae (a pathogenic trait of Candida). It is feasible that targeting virulence may emerge as a unique strategy in the process of developing nano silver-based treatments for clinical applications in fungal therapeutics because the transition from yeast to hypha is crucial for both virulence and the formation of biofilm [1-10].

Conclusion

As a result, one of the most important areas of research for antifungal drug optimization over the past 20 years has been the use of nanoparticlebased drug delivery techniques to increase the range of antifungal activity. These nanoparticles' main advantages are their small size and large surface area, which make them ideal replacements for a wide range of applications. The limitations of currently available drugs can also be significantly overcome by them. However, taking into account all of the research that has been done in this field, excluding the rare cases that have been described (such as liposomal amphotericin B, which is sold in nano-formulations), neither of these active substances has been shown to have any significant adverse effects. Currently, it is possible to buy ingredients in the market. This is mostly caused by the preclinical difficulties associated with the interventional studies as well as the problems with the use of these nanostructures.

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