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Pharmaceutics
Special Issues
Recent Advances in Antifungal Drugs
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Recent Advances in Antifungal Drugs

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (30 August 2022) | Viewed by 30448

Special Issue Editors

Prof. Dr. Maria José Soares Mendes Giannini

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Guest Editor
Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil
Interests: antifungal agents; biofilms; fungal-host interaction; nanotechonology
Special Issues, Collections and Topics in MDPI journals
Dr. Luigi Scipione

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Guest Editor
Department of Chemistry and Technologies of Drug, Sapienza University of Rome, 00185 Roma, Italy
Interests: drug design; metallophores; antifungal agents; antibiofilm compounds
Special Issues, Collections and Topics in MDPI journals
Dr. Marcia S.C. Melhem

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Guest Editor
1. School of Medicine,The Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil
2. Mycology Department, Adolfo Lutz Institute Center for Disease Control Secretary of Health, Sao Paulo 01246-000, SP, Brazil
Interests: antifungal agents; fungal infections; yeasts; molds
Special Issues, Collections and Topics in MDPI journals
Dr. Ana Marisa Fusco Almeida

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Guest Editor
School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, São Paulo 14800-903, Brazil
Interests: antifungal agents, biofilms, fungal-host interaction, nanotechonology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The arsenal of antifungal agents against fungal diseases is limited. Furthermore, most treatments are associated with side effects, drug interactions, harmful risks for pregnant women, or fungal resistance.

The high burden and increasing prevalence of both invasive and superficial fungal infections, associated with biofilm formation, toxicity, interactions related to current antifungals, as well as increased resistance, require the development of new antifungals—preferably with a new form of action. Additionally, the availability of oral alternatives or mode drug use would allow outpatient treatment, resulting in greater patient comfort and therapy adherence. Besides, when needed due to immunosuppression, associated therapies should also focus on further research.

Antifungals are clinically available to treat fungal infections, and primarily target ergosterol in the fungal cell membrane or 1,3-β-D-glucan in the fungal cell wall. These classes include polyenes, triazoles, and echinocandins. Although the newer antifungals and the improved formulations of others have advanced, our ability to treat patients with fungal infections is often limited by toxicity, drug interactions, and the need for intravenous administration in the case of systemic mycoses.

Therefore, this Special Issue intends to receive manuscripts that present advances in antifungals, new targets, new formulations that utilize novel delivery systems to enhance treatment efficacy and compliance, and new strategies to treat fungal infections.

Prof. Dr. Maria José Soares Mendes Giannini
Dr. Luigi Scipione
Dr. Marcia S.C. Melhem
Dr. Ana Marisa Fusco Almeida
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antifungal drugs
  • resistance
  • biofilms resistance
  • new targets
  • invasive fungal infections
  • superficial infections
  • pipeline
  • new formulations
  • treatment

Related Special Issue

Published Papers (12 papers)

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Research

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19 pages, 22384 KiB  
Article
Membranolytic Activity Profile of Nonyl 3,4-Dihydroxybenzoate: A New Anti-Biofilm Compound for the Treatment of Dermatophytosis
by Caroline B. Costa-Orlandi, Níura M. Bila, Jean Lucas C. Bonatti, Carolina O. Vaso, Mariana B. Santos, Carlos R. Polaquini, Mariana M. Santoni Biasioli, Rondinelli D. Herculano, Luis O. Regasini, Ana Marisa Fusco-Almeida and Maria José S. Mendes-Giannini
Pharmaceutics 2023, 15(5), 1402; https://doi.org/10.3390/pharmaceutics15051402 - 04 May 2023
Viewed by 1565
Abstract
The ability of dermatophytes to live in communities and resist antifungal drugs may explain treatment recurrence, especially in onychomycosis. Therefore, new molecules with reduced toxicity that target dermatophyte biofilms should be investigated. This study evaluated nonyl 3,4-dihydroxybenzoate (nonyl) susceptibility and mechanism of action [...] Read more.
The ability of dermatophytes to live in communities and resist antifungal drugs may explain treatment recurrence, especially in onychomycosis. Therefore, new molecules with reduced toxicity that target dermatophyte biofilms should be investigated. This study evaluated nonyl 3,4-dihydroxybenzoate (nonyl) susceptibility and mechanism of action on planktonic cells and biofilms of T. rubrum and T. mentagrophytes. Metabolic activities, ergosterol, and reactive oxygen species (ROS) were quantified, and the expression of genes encoding ergosterol was determined by real-time PCR. The effects on the biofilm structure were visualized using confocal electron microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). T. rubrum and T. mentagrophytes biofilms were susceptible to nonyl and resistant to fluconazole, griseofulvin (all strains), and terbinafine (two strains). The SEM results revealed that nonyl groups seriously damaged the biofilms, whereas synthetic drugs caused little or no damage and, in some cases, stimulated the development of resistance structures. Confocal microscopy showed a drastic reduction in biofilm thickness, and transmission electron microscopy results indicated that the compound promoted the derangement and formation of pores in the plasma membrane. Biochemical and molecular assays indicated that fungal membrane ergosterol is a nonyl target. These findings show that nonyl 3,4-dihydroxybenzoate is a promising antifungal compound. Full article
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
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15 pages, 295 KiB  
Article
Evaluation of the Sensititre YeastOne and Etest in Comparison with CLSI M38-A2 for Antifungal Susceptibility Testing of Three Azoles, Amphotericin B, Caspofungin, and Anidulafungin, against Aspergillusfumigatus and Other Species, Using New Clinical Breakpoints and Epidemiological Cutoff Values
by Marcia S. C. Melhem, Vivian C. Coelho, Claudia A. Fonseca, Lidiane de Oliveira, Lucas X. Bonfietti, Maria. W. Szeszs, Marcello M. C. Magri, Francine S. Dorneles, Hideaki Taguchi, Daniel V. S. Moreira, Adriana L. Motta, Marjorie V. Batista, Katsuhiko Kamei and Maria A. Shikanai-Yasuda
Pharmaceutics 2022, 14(10), 2161; https://doi.org/10.3390/pharmaceutics14102161 - 11 Oct 2022
Cited by 2 | Viewed by 1784
Abstract
Aspergillosis is an invasive fungal disease associated with high mortality. Antifungal susceptibility testing (AFST) is receiving increasing consideration for managing patients, as well as for surveilling emerging drug resistance, despite having time-consuming and technically complex reference methodologies. The Sensititre YeastOne (SYO) and Etest [...] Read more.
Aspergillosis is an invasive fungal disease associated with high mortality. Antifungal susceptibility testing (AFST) is receiving increasing consideration for managing patients, as well as for surveilling emerging drug resistance, despite having time-consuming and technically complex reference methodologies. The Sensititre YeastOne (SYO) and Etest methods are widely utilized for yeasts but have not been extensively evaluated for Aspergillus isolates. We obtained Posaconazole (POS), Voriconazole (VCZ), Itraconazole (ITC), Amphotericin B (AMB), Caspofungin (CAS), and Anidulafungin (AND) minimum inhibitory concentrations (MICs) for both the Etest (n = 330) and SYO (n = 339) methods for 106 sequenced clinical strains. For 84 A. fumigatus, we analyzed the performance of both commercial methods in comparison with the CLSI-AFST, using available cutoff values. An excellent correlation could be demonstrated for Etest-AMB and Etest-VCZ (p < 0.01). SYO-MICs of AMB, VCZ, and POS resulted in excellent essential agreement (>93%), and >80% for AMB, VCZ, and ITC Etest-MICs. High categoric agreement was found for AMB, ITC, and CAS Etest-MICs (>85%) and AMB SYO-MICs (>90%). The considerable number of major/very major errors found using Etest and SYO, possibly related to the proposed cutoffs and associated with the less time-consuming processes, support the need for the improvement of commercial methods for Aspergillus strains. Full article
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
17 pages, 4761 KiB  
Article
Characterization of the Secretome of Pathogenic Candida glabrata and Their Effectiveness against Systemic Candidiasis in BALB/c Mice for Vaccine Development
by Majid Rasool Kamli, Jamal S. M. Sabir, Maqsood Ahmad Malik and Aijaz Ahmad
Pharmaceutics 2022, 14(10), 1989; https://doi.org/10.3390/pharmaceutics14101989 - 21 Sep 2022
Cited by 4 | Viewed by 1725
Abstract
Infections by non-albicans Candida species have increased drastically in the past few decades. Candida glabrata is one of the most common opportunistic fungal pathogens in immunocompromised individuals, owing to its capability to attach to various human cell types and medical devices and being [...] Read more.
Infections by non-albicans Candida species have increased drastically in the past few decades. Candida glabrata is one of the most common opportunistic fungal pathogens in immunocompromised individuals, owing to its capability to attach to various human cell types and medical devices and being intrinsically weakly susceptible to azoles. Immunotherapy, including the development of antifungal vaccines, has been recognized as an alternative approach for preventing and treating fungal infections. Secretory proteins play a crucial role in establishing host–pathogen interactions and are also responsible for eliciting an immune response in the host during candidiasis. Therefore, fungal secretomes can provide promising protein candidates for antifungal vaccine development. This study attempts to uncover the presence of immunodominant antigenic proteins in the C. glabrata secretome and delineate their role in various biological processes and their potency in the development of antifungal vaccines. LC–MS/MS results uncovered that C. glabrata secretome consisted of 583 proteins, among which 33 were identified as antigenic proteins. The protection ability of secretory proteins against hematogenously disseminated infection caused by C. glabrata was evaluated in BALB/c mice. After immunization and booster doses, all the animals were challenged with a lethal dose of C. glabrata. All the mice showing signs of distress were sacrificed post-infection, and target organs were collected, followed by histopathology and C. glabrata (CFU/mg) estimation. Our results showed a lower fungal burden in target organs and increased survival in immunized mice compared to the infection control group, thus revealing the immunogenic property of secreted proteins. Thus, identified secretome proteins of C. glabrata have the potential to act as antigenic proteins, which can serve as potential candidates for the development of antifungal vaccines. This study also emphasizes the importance of a mass-spectrometry approach to identifying the antigenic proteins in C. glabrata secretome. Full article
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
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13 pages, 493 KiB  
Article
Combining Essential Oils with Each Other and with Clotrimazole Prevents the Formation of Candida Biofilms and Eradicates Mature Biofilms
by Rafael Alves da Silva, Nagela Bernadelli Sousa Silva, Carlos Henrique Gomes Martins, Regina Helena Pires, Denise Von Dolinger de Brito Röder and Reginaldo dos Santos Pedroso
Pharmaceutics 2022, 14(9), 1872; https://doi.org/10.3390/pharmaceutics14091872 - 05 Sep 2022
Cited by 1 | Viewed by 1289
Abstract
Fungal infections by Candida spp. are opportunistic and most often occur in individuals with some predisposing factor. Essential oils (EO) have anti-Candida potential, being a therapeutic alternative to be explored, especially for superficial and mucosal candidiasis. The objective was to analyze the [...] Read more.
Fungal infections by Candida spp. are opportunistic and most often occur in individuals with some predisposing factor. Essential oils (EO) have anti-Candida potential, being a therapeutic alternative to be explored, especially for superficial and mucosal candidiasis. The objective was to analyze the synergistic potential between the EO of Citrus limon, Cupressus sempervirens, Litsea cubeba and Melaleuca alternifolia, and each of them with clotrimazole, to inhibit in vitro the formation and eradication of Candida spp. biofilms. Added to this, the survival of Caenorhabditis elegans was evaluated after exposure to EO, clotrimazole and their synergistic combinations. Anti-Candida activity was determined by microdilution for the substances alone and in EO–EO and EO–clotrimazole combinations. The combinations were performed by the checkerboard method, and the reduction in the metabolic activity of biofilms was determined by the viability of MTT/menadione. C. elegans larvae survival was evaluated after 24 h of exposure to EO, clotrimazole and synergistic combinations. The minimum inhibitory concentration (MIC) of EO ranged from 500 to >4000 µg/mL. The lowest MIC (500 µg/mL) was for C. sempervirens and L. cubeba on a C. krusei isolate; for clotrimazole, the MIC ranged from 0.015 to 0.5 µg/mL. Biofilm inhibition and eradication both ranged from 1000 to >4000 µg/mL. The lethal concentration (LC50) of C. limon, L. cubeba and M. alternifolia was 2000 µg/mL for C. elegans, while for C. sempervirens and clotrimazole, it was not determined within the concentration limits tested. In combination, more than 85% of the larvae survived M. alternifolia–clotrimazole, M. alternifolia–L. cubeba, C. sempervirens–clotrimazole and C. sempervirens–C. limon combinations. This study is the first, to our knowledge, to present a synergistic relationship of EO–EO and EO–clotrimazole combinations on Candida spp. biofilms. Full article
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
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23 pages, 4964 KiB  
Article
Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures
by Carolina Orlando Vaso, Níura Madalena Bila, Fabiana Pandolfi, Daniela De Vita, Martina Bortolami, Jean Lucas Carvalho Bonatti, Rosângela Aparecida De Moraes Silva, Larissa Naiara Carvalho Gonçalves, Valeria Tudino, Roberta Costi, Roberto Di Santo, Maria José Soares Mendes-Giannini, Caroline Barcelos Costa-Orlandi, Luigi Scipione and Ana Marisa Fusco-Almeida
Pharmaceutics 2022, 14(5), 1043; https://doi.org/10.3390/pharmaceutics14051043 - 12 May 2022
Cited by 4 | Viewed by 2222
Abstract
Histoplasma capsulatum is a fungus that causes histoplasmosis. The increased evolution of microbial resistance and the adverse effects of current antifungals help new drugs to emerge. In this work, fifty-four nitrofurans and indoles were tested against the H. capsulatum EH-315 strain. Compounds with [...] Read more.
Histoplasma capsulatum is a fungus that causes histoplasmosis. The increased evolution of microbial resistance and the adverse effects of current antifungals help new drugs to emerge. In this work, fifty-four nitrofurans and indoles were tested against the H. capsulatum EH-315 strain. Compounds with a minimum inhibitory concentration (MIC90) equal to or lower than 7.81 µg/mL were selected to evaluate their MIC90 on ATCC G217-B strain and their minimum fungicide concentration (MFC) on both strains. The quantification of membrane ergosterol, cell wall integrity, the production of reactive oxygen species, and the induction of death by necrosis–apoptosis was performed to investigate the mechanism of action of compounds 7, 11, and 32. These compounds could reduce the extracted sterol and induce necrotic cell death, similarly to itraconazole. Moreover, 7 and 11 damaged the cell wall, causing flaws in the contour (11), or changing the size and shape of the fungal cell wall (7). Furthermore, 7 and 32 induced reactive oxygen species (ROS) formation higher than 11 and control. Finally, the cytotoxicity was measured in two models of cell culture, i.e., monolayers (cells are flat) and a three-dimensional (3D) model, where they present a spheroidal conformation. Cytotoxicity assays in the 3D model showed a lower toxicity in the compounds than those performed on cell monolayers. Overall, these results suggest that derivatives of nitrofurans and indoles are promising compounds for the treatment of histoplasmosis. Full article
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
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19 pages, 2068 KiB  
Article
Synthesis and Evaluation of the Antifungal and Toxicological Activity of Nitrofuran Derivatives
by Carolina Orlando Vaso, Fabiana Pandolfi, Níura Madalena Bila, Daniela De Vita, Martina Bortolami, Maria José Soares Mendes-Giannini, Valeria Tudino, Roberta Costi, Caroline Barcelos Costa-Orlandi, Ana Marisa Fusco-Almeida and Luigi Scipione
Pharmaceutics 2022, 14(3), 593; https://doi.org/10.3390/pharmaceutics14030593 - 08 Mar 2022
Cited by 3 | Viewed by 2230
Abstract
Fungal diseases affect more than 1 billion people worldwide. The constant global changes, the advent of new pandemics, and chronic diseases favor the diffusion of fungal pathogens such as Candida, Cryptococcus, Aspergillus, Trichophyton, Histoplasma capsulatum, and Paracoccidioides brasiliensis. [...] Read more.
Fungal diseases affect more than 1 billion people worldwide. The constant global changes, the advent of new pandemics, and chronic diseases favor the diffusion of fungal pathogens such as Candida, Cryptococcus, Aspergillus, Trichophyton, Histoplasma capsulatum, and Paracoccidioides brasiliensis. In this work, a series of nitrofuran derivatives were synthesized and tested against different fungal species; most of them showed inhibitory activity, fungicide, and fungistatic profile. The minimal inhibitory concentration (MIC90) values for the most potent compounds range from 0.48 µg/mL against H. capsulatum (compound 11) and P. brasiliensis (compounds 3 and 9) to 0.98 µg/mL against Trichophyton rubrum and T. mentagrophytes (compounds 8, 9, 12, 13 and 8, 12, 13, respectively), and 3.9 µg/mL against Candida and Cryptococcus neoformans strains (compounds 1 and 5, respectively). In addition, all compounds showed low toxicity when tested in vitro on lung cell lines (A549 and MRC-5) and in vivo in Caenorhabditis elegans larvae. Many of them showed high selectivity index values. Thus, these studied nitrofuran derivatives proved to be potent against different fungal species, characterized by low toxicity and high selectivity; for these reasons, they may become promising compounds for the treatment of mycoses. Full article
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
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10 pages, 968 KiB  
Communication
In Vitro Interaction and Killing-Kinetics of Amphotericin B Combined with Anidulafungin or Caspofungin against Candida auris
by Unai Caballero, Elena Eraso, Guillermo Quindós and Nerea Jauregizar
Pharmaceutics 2021, 13(9), 1333; https://doi.org/10.3390/pharmaceutics13091333 - 25 Aug 2021
Cited by 11 | Viewed by 2450
Abstract
Treatment of invasive infections caused by Candida auris is challenging due to the limited therapeutic options. The combination of antifungal drugs may be an interesting and feasible approach to be investigated. The aim of this study was to examine the in vitro activity [...] Read more.
Treatment of invasive infections caused by Candida auris is challenging due to the limited therapeutic options. The combination of antifungal drugs may be an interesting and feasible approach to be investigated. The aim of this study was to examine the in vitro activity of amphotericin B in combination with anidulafungin or caspofungin against C. auris. In vitro static time–kill curve experiments were conducted for 48 h with different combinations of amphotericin B with anidulafungin or caspofungin against six blood isolates of C. auris. The antifungal activity of 0.5 mg/L of amphotericin B was limited against the six isolates of C. auris. Similarly, echinocandins alone had a negligible effect, even at the highest tested concentrations. By contrast, 1 mg/L of amphotericin B showed fungistatic activity. Synergy was rapidly achieved (8 h) with 0.5 mg/L of amphotericin B plus 2 mg/L of anidulafungin or caspofungin. These combinations lead to a sustained fungistatic effect, and the fungicidal endpoint was reached against some C. auris isolates. Additionally, ≥0.5 mg/L of either of the two echinocandins with 1 mg/L of amphotericin B resulted in fungicidal effect against all C. auris isolates. In conclusion, combinations of amphotericin B with anidulafungin or caspofungin provided greater killing with a lower dose requirement for amphotericin B compared to monotherapy, with synergistic and/or fungicidal outcomes. Full article
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
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0 pages, 2568 KiB  
Article
RETRACTED: Development and Optimization of Luliconazole Spanlastics to Augment the Antifungal Activity against Candida albicans
by Nabil A. Alhakamy, Mohammed W. Al-Rabia, Shadab Md, Alaa Sirwi, Selwan Saud Khayat, Sahar Saad AlOtaibi, Raghad Abkar Hakami, Hadeel Al Sadoun, Basmah Medhat Eldakhakhny, Wesam H. Abdulaal, Hibah M. Aldawsari, Shaimaa M. Badr-Eldin and Mahmoud A. Elfaky
Pharmaceutics 2021, 13(7), 977; https://doi.org/10.3390/pharmaceutics13070977 - 28 Jun 2021
Cited by 13 | Viewed by 3395 | Retraction
Abstract
Luliconazole is a new topical imidazole antifungal drug for the treatment of skin infections. It has low solubility and poor skin penetration which limits its therapeutic applications. In order to improve its therapeutic efficacy, spanlastics nanoformulation was developed and optimized using a combined [...] Read more.
Luliconazole is a new topical imidazole antifungal drug for the treatment of skin infections. It has low solubility and poor skin penetration which limits its therapeutic applications. In order to improve its therapeutic efficacy, spanlastics nanoformulation was developed and optimized using a combined mixture-process variable design (CMPV). The optimized formulation was converted into a hydrogel formula to enhance skin penetration and increase the efficacy in experimental cutaneous Candida albicans infections in Swiss mice wounds. The optimized formulation was generated at percentages of Span and Tween of 48% and 52%, respectively, and a sonication time of 6.6 min. The software predicted that the proposed formulation would achieve a particle size of 50 nm with a desirability of 0.997. The entrapment of luliconazole within the spanlastics carrier showed significant (p < 0.0001) antifungal efficacy in the immunocompromised Candida-infected Swiss mice without causing any irritation, when compared to the luliconazole treated groups. The microscopic observation showed almost complete removal of the fungal colonies on the skin of the infected animals (0.2 ± 0.05 log CFU), whereas the control animals had 0.2 ± 0.05 log CFU. Therefore, luliconazole spanlastics could be an effective formulation with improved topical delivery for antifungal activity against C. albicans. Full article
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
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Review

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32 pages, 981 KiB  
Review
Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections
by Laís de Almeida Campos, Margani Taise Fin, Kelvin Sousa Santos, Marcos William de Lima Gualque, Ana Karla Lima Freire Cabral, Najeh Maissar Khalil, Ana Marisa Fusco-Almeida, Rubiana Mara Mainardes and Maria José Soares Mendes-Giannini
Pharmaceutics 2023, 15(1), 266; https://doi.org/10.3390/pharmaceutics15010266 - 12 Jan 2023
Cited by 1 | Viewed by 3014
Abstract
Invasive fungal infections increase mortality and morbidity rates worldwide. The treatment of these infections is still limited due to the low bioavailability and toxicity, requiring therapeutic monitoring, especially in the most severe cases. Voriconazole is an azole widely used to treat invasive aspergillosis, [...] Read more.
Invasive fungal infections increase mortality and morbidity rates worldwide. The treatment of these infections is still limited due to the low bioavailability and toxicity, requiring therapeutic monitoring, especially in the most severe cases. Voriconazole is an azole widely used to treat invasive aspergillosis, other hyaline molds, many dematiaceous molds, Candida spp., including those resistant to fluconazole, and for infections caused by endemic mycoses, in addition to those that occur in the central nervous system. However, despite its broad activity, using voriconazole has limitations related to its non-linear pharmacokinetics, leading to supratherapeutic doses and increased toxicity according to individual polymorphisms during its metabolism. In this sense, nanotechnology-based drug delivery systems have successfully improved the physicochemical and biological aspects of different classes of drugs, including antifungals. In this review, we highlighted recent work that has applied nanotechnology to deliver voriconazole. These systems allowed increased permeation and deposition of voriconazole in target tissues from a controlled and sustained release in different routes of administration such as ocular, pulmonary, oral, topical, and parenteral. Thus, nanotechnology application aiming to delivery voriconazole becomes a more effective and safer therapeutic alternative in the treatment of fungal infections. Full article
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
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28 pages, 1884 KiB  
Review
LncRNA: A Potential Target for Host-Directed Therapy of Candida Infection
by Ye Wang, Hongdan Xu, Na Chen, Jin Yang and Hongmei Zhou
Pharmaceutics 2022, 14(3), 621; https://doi.org/10.3390/pharmaceutics14030621 - 11 Mar 2022
Cited by 4 | Viewed by 3020
Abstract
Despite various drugs work against Candida, candidiasis represents clinical management challenges worldwide due to the rising incidence and recurrence rate, as well as epidemics, of new drug-resistant pathogens. Recent insights into interactions between Candida and hosts contribute to exploring novel therapeutic strategies, [...] Read more.
Despite various drugs work against Candida, candidiasis represents clinical management challenges worldwide due to the rising incidence and recurrence rate, as well as epidemics, of new drug-resistant pathogens. Recent insights into interactions between Candida and hosts contribute to exploring novel therapeutic strategies, termed host-directed therapies (HDTs). HDTs are viable adjuncts with good efficacy for the existing standard antifungal regimens. However, HDTs induce other response unintendedly, thus requiring molecular targets with highly specificity. Long noncoding RNAs (lncRNAs) with highly specific expression patterns could affect biological processes, including the immune response. Herein, this review will summarize recent advances of HDTs based on the Candida–host interaction. Especially, the findings and application strategies of lncRNAs related to the host response are emphasized. We propose it is feasible to target lncRNAs to modulate the host defense during Candida infection, which provides a new perspective in identifying options of HDTs for candidiasis. Full article
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
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18 pages, 666 KiB  
Review
Essential Oils of Melaleuca, Citrus, Cupressus, and Litsea for the Management of Infections Caused by Candida Species: A Systematic Review
by Rafael Alves da Silva, Flávia Maria Pinto Monteiro Antonieti, Denise Von Dolinger de Brito Röder and Reginaldo dos Santos Pedroso
Pharmaceutics 2021, 13(10), 1700; https://doi.org/10.3390/pharmaceutics13101700 - 15 Oct 2021
Cited by 4 | Viewed by 1961
Abstract
Candida is a common agent of infection in humans, which has a wide distribution and is a colonizer fungus of the body, occasionally assuming the role of a pathogen. The type of treatment depends on the site of infection and the clinical condition [...] Read more.
Candida is a common agent of infection in humans, which has a wide distribution and is a colonizer fungus of the body, occasionally assuming the role of a pathogen. The type of treatment depends on the site of infection and the clinical condition of the patient. Superficial infections, such as mucosal infections, can be treated with topical medications. So-called alternative therapies have rarely been studied, although the literature records the effectiveness of some treatments, especially as complementary therapy. The aims of this review were to analyze evidence of the anti-Candida inhibitory activity of essential oils of the Citrus, Cupressus, Litsea, and Melaleuca species; in addition to addressing the chemical composition, probable mechanisms of antifungal action and studies of toxicity, cytotoxicity, and genotoxicity were included. The literature from Medline/PubMed, Science Direct, Scopus, Web of Science, and the Brazilian database Periodic Capes was reviewed. Thirty-eight articles were selected, which included two articles on Litsea spp., seven on Cupressus spp., thirteen articles on Citrus spp., and twenty-one articles on Melaleuca spp. In conclusion, this study showed in vitro evidence for the use of essential oils of the plant species evaluated for the treatment of infections caused by different Candida species. Full article
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
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18 pages, 2504 KiB  
Review
Biomaterials for the Prevention of Oral Candidiasis Development
by Dan Cristian Gheorghe, Adelina-Gabriela Niculescu, Alexandra Cătălina Bîrcă and Alexandru Mihai Grumezescu
Pharmaceutics 2021, 13(6), 803; https://doi.org/10.3390/pharmaceutics13060803 - 27 May 2021
Cited by 15 | Viewed by 4375
Abstract
Thousands of microorganisms coexist within the human microbiota. However, certain conditions can predispose the organism to the overgrowth of specific pathogens that further lead to opportunistic infections. One of the most common such imbalances in the normal oral flora is the excessive growth [...] Read more.
Thousands of microorganisms coexist within the human microbiota. However, certain conditions can predispose the organism to the overgrowth of specific pathogens that further lead to opportunistic infections. One of the most common such imbalances in the normal oral flora is the excessive growth of Candida spp., which produces oral candidiasis. In immunocompromised individuals, this fungal infection can reach the systemic level and become life-threatening. Hence, prompt and efficient treatment must be administered. Traditional antifungal agents, such as polyenes, azoles, and echinocandins, may often result in severe adverse effects, regardless of the administration form. Therefore, novel treatments have to be developed and implemented in clinical practice. In this regard, the present paper focuses on the newest therapeutic options against oral Candida infections, reviewing compounds and biomaterials with inherent antifungal properties, improved materials for dental prostheses and denture adhesives, drug delivery systems, and combined approaches towards developing the optimum treatment. Full article
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
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