scholarly journals Striking Back against Fungal Infections: The Utilization of Nanosystems for Antifungal Strategies

2021 ◽  
Vol 22 (18) ◽  
pp. 10104
Author(s):  
Wei Du ◽  
Yiru Gao ◽  
Li Liu ◽  
Sixiang Sai ◽  
Chen Ding
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Water Solubility ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Aspergillus Species ◽  
Health Concern ◽  
Tissue Penetration ◽  
Major Health ◽  
Invasive Infections

Fungal infections have become a major health concern, given that invasive infections by Candida, Cryptococcus, and Aspergillus species have led to millions of mortalities. Conventional antifungal drugs including polyenes, echinocandins, azoles, allylamins, and antimetabolites have been used for decades, but their limitations include off-target toxicity, drug-resistance, poor water solubility, low bioavailability, and weak tissue penetration, which cannot be ignored. These drawbacks have led to the emergence of novel antifungal therapies. In this review, we discuss the nanosystems that are currently utilized for drug delivery and the application of antifungal therapies.

Recent Advances in Azole Based Scaffolds as Anticandidal Agents

2019 ◽  
Vol 16 (5) ◽  
pp. 492-501 ◽  
Author(s):  
Prabhuodeyara Math Gurubasavaraj ◽  
Jasmith Shivayya Charantimath
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Candida Albicans ◽  
Drug Interactions ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Fungal Virulence ◽  
Compromised Patients

Aim:The present review aims to explore the development of novel antifungal agents, such as pharmacology, pharmacokinetics, spectrum of activity, safety, toxicity and other aspects that involve drug-drug interactions of the azole antifungal agents.Introduction:Fungal infections in critically ill and immune-compromised patients are increasing at alarming rates, caused mainly by Candida albicans an opportunistic fungus. Despite antifungal annihilators like amphotericin B, azoles and caspofungin, these infections are enormously increasing. The unconventional increase in such patients is a challenging task for the management of antifungal infections especially Candidiasis. Moreover, problem of toxicity associated with antifungal drugs on hosts and rise of drug-resistance in primary and opportunistic fungal pathogens has obstructed the success of antifungal therapy.Conclusion:Hence, to conflict these problems new antifungal agents with advanced efficacy, new formulations of drug delivery and novel compounds which can interact with fungal virulence are developed and used to treat antifungal infections.

Strategies of Drug Delivery for Deep Fungal Infection: A Review

2020 ◽  
Vol 8 (5) ◽  
pp. 372-390
Author(s):  
Zhongyi Ma ◽  
Xiaoyou Wang ◽  
Chong Li
Keyword(s):  
Drug Delivery ◽  
Fungal Infection ◽  
Antifungal Agents ◽  
Water Solubility ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Treatment Needs ◽  
Drug Bioavailability ◽  
Delivery Strategies ◽  
Deep Fungal Infection

: The deep fungal infection poses serious threats to human health, mainly due to the increase in the number of immunocompromised individuals. Current first-line antifungal agents such as Amphotericin B, Fluconazole and Itraconazole, may decrease the severity of fungal infection to some extent, but the poor drug bioavailability, drug toxicity and poor water solubility seriously restrict their clinical utility. This review focuses on the study of drug delivery strategies for the treatment of deep fungal infections. We summarize the drug delivery strategies recently reported for the treatment of deep fungal infection, and explain each part with research examples. We discuss the use of pharmaceutical approaches to improve the physicochemical properties of the antifungal drugs to provide a basis for the clinical application of antifungal drugs. We then highlight the strategies for targeting drug delivery to the infection sites of fungi and fungal surface moieties, which have the potential to get developed as clinically relevant targeted therapies against deep fungal infections. It is worth noting that the current research on fungal infections still lags behind the research on other pathogens, and the drug delivery strategy for the treatment of deep fungal infections is far from meeting the treatment needs. Therefore, we envision the potential strategies inspired by the treatment of diseases with referential pathology or pathophysiology, further enriching the delivery of antifungal agents, providing references for basic research of fungal infections. Lay Summary: The deep fungal infections pose serious threats to the health of immunodeficiency patients. It is worth noting that the current research on fungi is still lagging behind that on other pathogens. The drug delivery strategies for the treatment of deep fungal infections are far from meeting the treatment needs. We summarize the recently reported drug delivery strategies for treating deep fungal infection, and envision the potential strategies to further enrich the delivery of antifungal agents.

scholarly journals Linking Cellular Morphogenesis with Antifungal Treatment and Susceptibility in Candida Pathogens

2019 ◽  
Vol 5 (1) ◽  
pp. 17 ◽  
Author(s):  
Jehoshua Sharma ◽  
Sierra Rosiana ◽  
Iqra Razzaq ◽  
Rebecca Shapiro
Keyword(s):  
Drug Resistance ◽  
Candida Species ◽  
Cellular Response ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Health Concern ◽  
Biofilm Growth ◽  
Antifungal Drug Resistance

Fungal infections are a growing public health concern, and an increasingly important cause of human mortality, with Candida species being amongst the most frequently encountered of these opportunistic fungal pathogens. Several Candida species are polymorphic, and able to transition between distinct morphological states, including yeast, hyphal, and pseudohyphal forms. While not all Candida pathogens are polymorphic, the ability to undergo morphogenesis is linked with the virulence of many of these pathogens. There are also many connections between Candida morphogenesis and antifungal drug treatment and susceptibility. Here, we review how Candida morphogenesis—a key virulence trait—is linked with antifungal drugs and antifungal drug resistance. We highlight how antifungal therapeutics are able to modulate morphogenesis in both sensitive and drug-resistant Candida strains, the shared signaling pathways that mediate both morphogenesis and the cellular response to antifungal drugs and drug resistance, and the connection between Candida morphology, drug resistance, and biofilm growth. We further review the development of anti-virulence drugs, and targeting Candida morphogenesis as a novel therapeutic strategy to target fungal pathogens. Together, this review highlights important connections between fungal morphogenesis, virulence, and susceptibility to antifungals.

Elegant flexible vesicular nanocarriers for the efficient skin delivery of topically applied drugs-

2021 ◽  
Vol 18 ◽  
Author(s):  
Waleed Albalawi ◽  
Surur Alharbi ◽  
Fahad Alanazi ◽  
Hameed Alahmadi ◽  
Mothib Alghamdi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Skin Diseases ◽  
Fungal Infections ◽  
Skin Barrier ◽  
Therapeutic Outcome ◽  
Health Concern ◽  
Inflammatory Skin Diseases ◽  
Skin Delivery ◽  
Pubmed Database ◽  
Vesicular Carriers

Background: Skin diseases represent a major health concern worldwide and negatively impact patients’ quality of life. Despite the availability of various efficacious drugs, their therapeutic outcome is often limited due to shortcomings related to the formidable skin barrier and unfavorable physicochemical properties of drugs. Flexible nano-vesicles have shown tremendous potential to overcome these hurdles and improve the local therapeutic effect of these drugs. Objective: This review article is aimed to shed light on flexible nano-vesicular carriers as a means to combat skin diseases. Methods: The literature was reviewed using PubMed database using various keywords such as liposomes, flexible (deformable liposomes) (transferosomes), ethosomes, transethosomes, niosomes, and spanlastics. Results: Liposomes and niosomes were found effective for the loading and release of both hydrophilic and lipophilic drugs. However, their limited skin penetration led to drug delivery to the outermost layers of skin only. This necessitates the search for innovative vesicular carriers, including liposomes, flexible (deformable liposomes), ethosomes, transethosomes, and spanlastics. These flexible nano-vesicular carriers showed enhanced drug delivery and deposition across various skin layers, which was better than their corresponding conventional vesicles. This resulted in superior drug efficacy against various skin diseases such as skin cancer, inflammatory skin diseases, superficial fungal infections, etc. Conclusion: Flexible nano-vesicular carriers have proven themselves as efficient drug delivery systems that are able to deliver their cargo into the deep skin layers and thus, improve the therapeutic outcome of various skin diseases. However, there remain some challenges that need to be addressed before these nanocarriers can be translated from the lab to clinics.

scholarly journals Application of Dendrimers for the Treatment of Infectious Diseases

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2205 ◽  
Author(s):  
Zandile Mhlwatika ◽  
Blessing Aderibigbe
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Infectious Diseases ◽  
Water Solubility ◽  
Three Dimensional ◽  
Parasitic Infections ◽  
Release Mechanism ◽  
Macromolecular Network ◽  
And Control ◽  
Drug Encapsulation Efficiency

Dendrimers are drug delivery systems that are characterized by a three-dimensional, star-shaped, branched macromolecular network. They possess ideal properties such as low polydispersity index, biocompatibility and good water solubility. They are made up of the interior and the exterior layers. The exterior layer consists of functional groups that are useful for conjugation of drugs and targeting moieties. The interior layer exhibits improved drug encapsulation efficiency, reduced drug toxicity, and controlled release mechanisms. These unique properties make them useful for drug delivery. Dendrimers have attracted considerable attention as drug delivery system for the treatment of infectious diseases. The treatment of infectious diseases is hampered severely by drug resistance. Several properties of dendrimers such as their ability to overcome drug resistance, toxicity and control the release mechanism of the encapsulated drugs make them ideal systems for the treatment of infectious disease. The aim of this review is to discuss the potentials of dendrimers for the treatment of viral and parasitic infections.

Progress and prospects for targeting Hsp90 to treat fungal infections

Parasitology ◽  
2014 ◽  
Vol 141 (9) ◽  
pp. 1127-1137 ◽  
Author(s):  
AMANDA VERI ◽  
LEAH E. COWEN
Keyword(s):  
Drug Resistance ◽  
Anticancer Agents ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Effective Combination ◽  
New Strategy ◽  
Life Threatening ◽  
Hsp90 Chaperone ◽  
Hsp90 Function

SummaryFungal pathogens pose a major threat to human health worldwide. They infect billions of people each year, leading to at least 1·5 million deaths. Treatment of fungal infections is difficult due to the limited number of clinically useful antifungal drugs, and the emergence of drug resistance. A promising new strategy to enhance the efficacy of antifungal drugs and block the evolution of drug resistance is to target the molecular chaperone Hsp90. Pharmacological inhibitors of Hsp90 function that are in development as anticancer agents have potential to be repurposed as agents for combination antifungal therapy for some applications, such as biofilm infections. For systemic infections, however, effective combination therapy regimens may require Hsp90 inhibitors that can selectively target Hsp90 in the pathogen, or alternate strategies to compromise function of the Hsp90 chaperone machine. Selectively impairing Hsp90 function in the pathogen could in principle be achieved by targeting Hsp90 co-chaperones or regulators of Hsp90 function that are more divergent between pathogen and host than Hsp90. Antifungal combination therapies could also exploit downstream effectors of Hsp90 that are critical for fungal drug resistance and virulence. Here, we discuss the progress and prospects for establishing Hsp90 as an important therapeutic target for life-threatening fungal infections.

scholarly journals Antifungal and Anti-Inflammatory Potential of Bupleurum rigidum subsp. paniculatum (Brot.) H.Wolff Essential Oil

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 592
Author(s):  
Mónica Zuzarte ◽  
Pedro M. P. Correia ◽  
Jorge M. Alves-Silva ◽  
Maria J. Gonçalves ◽  
Carlos Cavaleiro ◽  
...  
Keyword(s):  
Essential Oil ◽  
Fungal Infections ◽  
Health Concern ◽  
Major Health ◽  
Transmission Electron ◽  
Anti Inflammatory ◽  
Bioactive Potential ◽  
Effective Drugs ◽  
First Time ◽  
Oxide Inhibition

Fungal infections remain a major health concern with aromatic plants and their metabolites standing out as promising antifungal agents. The present study aims to assess, for the first time, the antifungal and anti-inflammatory potential of Bupleurum subsp. paniculatum (Brot.) H.Wolff essential oil from Portugal. The oil obtained by hydrodistillation and characterized by GC-MS, showed high amounts of monoterpene hydrocarbons, namely α-pinene (29.0–36.0%), β–pinene (26.1–30.7%) and limonene (10.5–13.5%). The antifungal potential was assessed, according to CLSI guidelines, against several clinical and collection strains. The essential oil showed a broad fungicidal effect being more potent against Cryptococcus neoformans and dermatophytes. Moreover, a significant germ tube inhibition was observed in Candida albicans as well as a disruption of mature biofilms, thus pointing out an effect of the oil against relevant virulent factors. Furthermore, fungal ultrastructural modifications were detected through transmission electron microscopy, highlighting the nefarious effect of the oil. Of relevance, the oil also evidenced anti-inflammatory activity through nitric oxide inhibition in macrophages activated with lipopolysaccharide. In addition, the essential oil’s bioactive concentrations did not present toxicity towards macrophages. Overall, the present study confirmed the bioactive potential of B. rigidum subsp. paniculatum essential oil, thus paving the way for the development of effective drugs presenting concomitantly antifungal and anti-inflammatory properties.

scholarly journals Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 461 ◽  
Author(s):  
Ewa Ksiezopolska ◽  
Toni Gabaldón
Keyword(s):  
Drug Resistance ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Developed Countries ◽  
Antifungal Drugs ◽  
Opportunistic Pathogens ◽  
Evolutionary Mechanisms

Fungal infections, such as candidiasis caused by Candida, pose a problem of growing medical concern. In developed countries, the incidence of Candida infections is increasing due to the higher survival of susceptible populations, such as immunocompromised patients or the elderly. Existing treatment options are limited to few antifungal drug families with efficacies that vary depending on the infecting species. In this context, the emergence and spread of resistant Candida isolates are being increasingly reported. Understanding how resistance can evolve within naturally susceptible species is key to developing novel, more effective treatment strategies. However, in contrast to the situation of antibiotic resistance in bacteria, few studies have focused on the evolutionary mechanisms leading to drug resistance in fungal species. In this review, we will survey and discuss current knowledge on the genetic bases of resistance to antifungal drugs in Candida opportunistic pathogens. We will do so from an evolutionary genomics perspective, focusing on the possible evolutionary paths that may lead to the emergence and selection of the resistant phenotype. Finally, we will discuss the potential of future studies enabled by current developments in sequencing technologies, in vitro evolution approaches, and the analysis of serial clinical isolates.

Antimycotic drugs and their mechanisms of resistance to Candida species

2021 ◽  
Vol 22 ◽  
Author(s):  
Sweety Dahiya ◽  
Namita Sharma ◽  
Aruna Punia ◽  
Pooja Choudhary ◽  
Prity Gulia ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Candida Species ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Treatment Strategies ◽  
Distinct Species ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Success Rates ◽  
Antifungal Drug Resistance

: Fungal infections have shown an upsurge in recent decades, mainly because of the increasing number of immunocompromised patients, and the occurrence of invasive candidiasis is found to be 7-15 folds greater than that of invasive aspergillosis. The genus Candida comprises of more than 150 distinct species; however, only a few of them are found to be pathogenic to humans. Mortality rates of Candida species are found to be around 45%, and the reasons for this intensified mortality are inefficient diagnostic techniques and unfitting initial treatment strategies. There are only a few antifungal drug classes that are employed for the remedy of invasive fungal infections, including azoles, polyenes, echinocandins, and pyrimidine analogs. During the last 2-3 decades, the usage of antifungal drugs has increased several folds, due to which the reports of escalating antifungal drug resistance have also been recorded. The resistance is mostly to the triazole-based compounds. Due to antifungal drug resistance, the success rates of treatment have been reduced and major changes have been observed in the frequency of fungal infections. In this review, we have summarized the major molecular mechanisms for the development of antifungal drug resistance.

Exploration of Medicinal Plants as Sources of Novel Anticandidal Drugs

2019 ◽  
Vol 19 (28) ◽  
pp. 2579-2592
Author(s):  
Ajay Kumar ◽  
Feroz Khan ◽  
Dharmendra Saikia
Keyword(s):  
Drug Resistance ◽  
Medicinal Plants ◽  
Fungal Infections ◽  
Relevant Information ◽  
Antifungal Drugs ◽  
Fungal Strains ◽  
Efficient Management ◽  
Mucosal Surfaces ◽  
Human Infections ◽  
Anti Fungal

Background: : Human infections associated with skin and mucosal surfaces, mainly in tropical and sub-tropical parts of the world. During the last decade, there have been an increasing numbers of cases of fungal infections in immunocompromised patients, coupled with an increase in the number of incidences of drug resistance and toxicity to anti fungal agents. Hence, there is a dire need for safe, potent and affordable new antifungal drugs for the efficient management of candidal infections with minimum or no side effects. Introduction: : Candidiasis represents a critical problem to human health and a serious concern worldwide. Due to the development of drug resistance, there is a need for new antifungal agents. Therefore, we reviewed the different medicinal plants as sources of novel anticandidal drugs. Methods: : The comprehensive and detailed literature on medicinal plants was carried out using different databases, such as Google Scholar, PubMed, and Science Direct and all the relevant information from the articles were analyzed and included. Result: : Relevant Publications up to the end of November 2018, reporting anticandidal activity of medicinal plants has been included in the present review. In the present study, we have reviewed in the light of SAR and mechanisms of action of those plants whose extracts or phytomolecules are active against candida strains. Conclusion:: This article reviewed natural anticandidal drugs of plant origin and also summarized the potent antifungal bioactivity against fungal strains. Besides, mechanism of action of these potent active plant molecules was also explored for a comparative study. We concluded that the studied active plant molecules exhibit potential antifungal activity against resistant fungal strains.

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