scholarly journals Synergism of Zinc Oxide Quantum Dots with Antifungal Drugs: Potential Approach for Combination Therapy against Drug Resistant Candida albicans

2021 ◽  
Vol 3 ◽  
Author(s):  
Preeti Chand ◽  
Sangeeta Kumari ◽  
Neelima Mondal ◽  
Surinder P. Singh ◽  
Tulika Prasad
Keyword(s):  
Quantum Dots ◽  
Drug Resistance ◽  
Zinc Oxide ◽  
Candida Albicans ◽  
Combination Therapy ◽  
Antifungal Drugs ◽  
Low Concentrations ◽  
Drug Doses ◽  
Zno Qds

Candidiasis caused by Candida albicans is one of the most common microbial infections. Azoles, polyenes, allylamines, and echinocandins are classes of antifungals used for treating Candida infections. Standard drug doses often become ineffective due to the emergence of multidrug resistance (MDR). This leads to the use of higher drug doses for prolonged duration, resulting in severe toxicity (nephrotoxicity and liver damage) in humans. However, combination therapy using very low concentrations of two or more antifungal agents together, can lower such toxicity and limit evolution of drug resistance. Herein, 4–6 nm zinc oxide quantum dots (ZnO QDs) were synthesized and their in vitro antifungal activities were assessed against drug-susceptible (G1, F1, and GU4) and resistant (G5, F5, and GU5) isolates of C. albicans. In broth microdilution assay, ZnO QDs exhibited dose dependent growth inhibition between 0 – 200 µg/ml and almost 90% growth was inhibited in all Candida strains at 200 µg/ml of ZnO QDs. Synergy between ZnO QDs and antifungal drugs at sub-inhibitory concentrations of each was assessed by checkerboard analysis and expressed in terms of the fractional inhibitory concentration (FIC) index. ZnO QDs were used with two different classes of antifungals (azoles and polyenes) against Candida isolates: combination 1 (with fluconazole); combination 2 (with ketoconazole); combination 3 (with amphotericin B), and combination 4 (with nystatin). Results demonstrated that the potency of combinations of ZnO QDs with antifungal drugs even at very low concentrations of each was higher than their individual activities against the fungal isolates. The FIC index was found to be less than 0.5 for all combinations in the checkerboard assay, which confirmed synergism between sub-inhibitory concentrations of ZnO QDs (25 µg/ml) and individual antifungal drugs. Synergism was further confirmed by spot assay where cell viabilities of Candida strains were significantly reduced in all combinations, which was clearly evident from the disappearance of fungal cells on agar plates containing antifungal combinations. For safer clinical use, the in vitro cytotoxic activity of ZnO QDs was assessed against HeLa cell line and it was found that ZnO QDs were non-toxic at 25 µg/ml. Results suggested that the combination of ZnO QDs with drugs potentiate antimicrobial activity through multitargeted action. ZnO QDs could therefore offer a versatile alternative in combination therapy against MDR fungal pathogens, wherein lowering drug concentrations could reduce toxicity and their multitargeted action could limit evolution of fungal drug resistance.

scholarly journals Synthesis and Characterization of Polyvinylpyrrolidone-Modified ZnO Quantum Dots and Their In Vitro Photodynamic Tumor Suppressive Action

2021 ◽  
Vol 22 (15) ◽  
pp. 8106
Author(s):  
Tianming Song ◽  
Yawei Qu ◽  
Zhe Ren ◽  
Shuang Yu ◽  
Mingjian Sun ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Photodynamic Therapy ◽  
Inhibitory Effect ◽  
Therapeutic Effects ◽  
In Vivo Experiments ◽  
Potential Applications ◽  
Zno Quantum Dots ◽  
Zno Qds

Despite the numerous available treatments for cancer, many patients succumb to side effects and reoccurrence. Zinc oxide (ZnO) quantum dots (QDs) are inexpensive inorganic nanomaterials with potential applications in photodynamic therapy. To verify the photoluminescence of ZnO QDs and determine their inhibitory effect on tumors, we synthesized and characterized ZnO QDs modified with polyvinylpyrrolidone. The photoluminescent properties and reactive oxygen species levels of these ZnO/PVP QDs were also measured. Finally, in vitro and in vivo experiments were performed to test their photodynamic therapeutic effects in SW480 cancer cells and female nude mice. Our results indicate that the ZnO QDs had good photoluminescence and exerted an obvious inhibitory effect on SW480 tumor cells. These findings illustrate the potential applications of ZnO QDs in the fields of photoluminescence and photodynamic therapy.

scholarly journals In Vitro Synergistic Interactions of Isavuconazole and Echinocandins against Candida auris

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 355
Author(s):  
Unai Caballero ◽  
Sarah Kim ◽  
Elena Eraso ◽  
Guillermo Quindós ◽  
Valvanera Vozmediano ◽  
...  
Keyword(s):  
Interaction Model ◽  
Antifungal Drugs ◽  
Health Concern ◽  
Candida Auris ◽  
Fungistatic Activity ◽  
Drug Concentrations ◽  
Low Concentrations ◽  
Wide Range ◽  
Time Kill

Candida auris is an emergent fungal pathogen that causes severe infectious outbreaks globally. The public health concern when dealing with this pathogen is mainly due to reduced susceptibility to current antifungal drugs. A valuable alternative to overcome this problem is to investigate the efficacy of combination therapy. The aim of this study was to determine the in vitro interactions of isavuconazole with echinocandins against C. auris. Interactions were determined using a checkerboard method, and absorbance data were analyzed with different approaches: the fractional inhibitory concentration index (FICI), Greco universal response surface approach, and Bliss interaction model. All models were in accordance and showed that combinations of isavuconazole with echinocandins resulted in an overall synergistic interaction. A wide range of concentrations within the therapeutic range were selected to perform time-kill curves. These confirmed that isavuconazole–echinocandin combinations were more effective than monotherapy regimens. Synergism and fungistatic activity were achieved with combinations that included isavuconazole in low concentrations (≥0.125 mg/L) and ≥1 mg/L of echinocandin. Time-kill curves revealed that once synergy was achieved, combinations of higher drug concentrations did not improve the antifungal activity. This work launches promising results regarding the combination of isavuconazole with echinocandins for the treatment of C. auris infections.

scholarly journals CaNdt80 Is Involved in Drug Resistance in Candida albicans by Regulating CDR1

2004 ◽  
Vol 48 (12) ◽  
pp. 4505-4512 ◽  
Author(s):  
Chia-Geun Chen ◽  
Yun-Liang Yang ◽  
Hsin-I Shih ◽  
Chia-Li Su ◽  
Hsiu-Jung Lo
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Resistance ◽  
Candida Albicans ◽  
Type Strain ◽  
Antifungal Agents ◽  
Wild Type Strain ◽  
Efflux Pump ◽  
Antifungal Drugs ◽  
Galactosidase Activity ◽  
Wild Type

ABSTRACT Overexpression of CDR1, an efflux pump, is one of the major mechanisms contributing to drug resistance in Candida albicans. CDR1 p-lacZ was constructed and transformed into a Saccharomyces cerevisiae strain so that the lacZ gene could be used as the reporter to monitor the activity of the CDR1 promoter. Overexpression of CaNDT80, the C. albicans homolog of S. cerevisiae NDT80, increases the β-galactosidase activity of the CDR1 p-lacZ construct in S. cerevisiae. Furthermore, mutations in CaNDT80 abolish the induction of CDR1 expression by antifungal agents in C. albicans. Consistently, the Candt80/Candt80 mutant is also more susceptible to antifungal drugs than the wild-type strain. Thus, the gene for CaNdt80 may be the first gene among the regulatory factors involved in drug resistance in C. albicans whose function has been identified.

scholarly journals In vitro activity of zinc oxide-eugenol and glass ionomer cements on Candida albicans

2005 ◽  
Vol 19 (2) ◽  
pp. 134-138 ◽  
Author(s):  
Anna Carolina Aguiar Cassanho ◽  
Aletéia Massula Fernandes ◽  
Luciane Dias de Oliveira ◽  
Claudio Antonio Talge Carvalho ◽  
Antonio Olavo Cardoso Jorge ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Candida Albicans ◽  
Control Group ◽  
Glass Ionomer ◽  
Experimental Conditions ◽  
Mean Values ◽  
Zinc Oxide Eugenol ◽  
Colony Forming Units ◽  
And Control

The aim of this study was to evaluate in vitro the antimicrobial activity of glass ionomer (GIC) and zinc oxide-eugenol (ZOE) cements against Candida albicans. Standardized GIC and ZOE specimens were maintained in contact with C. albicans suspension (1 <FONT FACE=Symbol>´</FONT> 10(6) cells/ml) at 37°C for 24 h, 48 h or 7 days. A control group without any testing cement was included. After the incubation period, aliquots of 0.1 ml were plated on Sabouraud's agar, and then the number of colonies was counted. The results were expressed as values of logarithms of colony-forming units per milliliter (log CFU/mL) and were analyzed statistically by Kruskal-Wallis ANOVA. After 48 h of incubation, the ZOE group presented no growth of C. albicans. GIC and control groups presented similar mean values at all tested periods. According to the results obtained, it could be concluded that, under the experimental conditions, ZOE cement was more effective in vitro against C. albicans than GIC.

scholarly journals Artemisinin-independent inhibitory activity of Artemisia sp. infusions against different Plasmodium stages including relapse-causing hypnozoites

2021 ◽  
Vol 5 (3) ◽  
pp. e202101237
Author(s):  
Kutub Ashraf ◽  
Shahin Tajeri ◽  
Christophe-Sébastien Arnold ◽  
Nadia Amanzougaghene ◽  
Jean-François Franetich ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Inhibitory Activity ◽  
Parasite Species ◽  
Artemisia Annua ◽  
Combination Therapies ◽  
Lead Compounds ◽  
Low Concentrations ◽  
Inhibitory Activities

Artemisinin-based combination therapies (ACT) are the frontline treatments against malaria worldwide. Recently the use of traditional infusions from Artemisia annua (from which artemisinin is obtained) or Artemisia afra (lacking artemisinin) has been controversially advocated. Such unregulated plant-based remedies are strongly discouraged as they might constitute sub-optimal therapies and promote drug resistance. Here, we conducted the first comparative study of the anti-malarial effects of both plant infusions in vitro against the asexual erythrocytic stages of Plasmodium falciparum and the pre-erythrocytic (i.e., liver) stages of various Plasmodium species. Low concentrations of either infusion accounted for significant inhibitory activities across every parasite species and stage studied. We show that these antiplasmodial effects were essentially artemisinin-independent and were additionally monitored by observations of the parasite apicoplast and mitochondrion. In particular, the infusions significantly incapacitated sporozoites, and for Plasmodium vivax and P. cynomolgi, disrupted the hypnozoites. This provides the first indication that compounds other than 8-aminoquinolines could be effective antimalarials against relapsing parasites. These observations advocate for further screening to uncover urgently needed novel antimalarial lead compounds.

scholarly journals Anti-Candidal Activity and In Vitro Cytotoxicity Assessment of Graphene Nanoplatelets Decorated with Zinc Oxide Nanorods

Nanomaterials ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 752 ◽  
Author(s):  
Graziella Ficociello ◽  
Maria De Caris ◽  
Giusy Trillò ◽  
Domenico Cavallini ◽  
Maria Sarto ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Candida Albicans ◽  
Pathogenic Fungus ◽  
In Vitro Cytotoxicity ◽  
Yeast Cells ◽  
Zinc Oxide Nanorods ◽  
Aggregation State ◽  
Oxide Nanorods ◽  
Biofilm Development

Candida albicans is the most common pathogenic fungus that is isolated in nosocomial infections in medically and immune-compromised patients. The ability of C. albicans to convert its form from yeast to hyphal morphology contributes to biofilm development that effectively shelters Candida against the action of antifungals molecules. In the last years, nanocomposites are the most promising solutions against drug-resistant microorganisms. The aim of this study was to investigate the antifungal activity of graphene nanoplateles decorated with zinc oxide nanorods (ZNGs) against the human pathogen Candida albicans. We observed that ZNGs were able to induce a significant mortality in fungal cells, as well as to affect the main virulence factors of this fungus or rather the hyphal development and biofilm formation. Reactive Oxygen Species (ROS) formation in yeast cells resulted one of the mechanisms of ZNGs to induce mortality. Finally, the toxicity of this nanomaterial was tested also on human keratinocyte cell line HaCaT. Our data indicated that ZNGs resulted not toxic when their aggregation state decreased by adding glycerol as emulsifier to ZNGs suspensions or when HaCaT cells were grown on ZNGs-coated glasses. Overall, the results that were obtained indicated that ZNGs could be exploited as an antifungal nanomaterial with a high degree of biocompatibility on human cells.

scholarly journals In Vitro Antifungal Activities of a Series of Dication-Substituted Carbazoles, Furans, and Benzimidazoles

1998 ◽  
Vol 42 (10) ◽  
pp. 2503-2510 ◽  
Author(s):  
Maurizio Del Poeta ◽  
Wiley A. Schell ◽  
Christine C. Dykstra ◽  
Susan K. Jones ◽  
Richard R. Tidwell ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Fusarium Solani ◽  
Antifungal Agents ◽  
Antifungal Drugs ◽  
Inhibitory Compounds ◽  
Wide Range ◽  
Fluconazole Resistant ◽  
Resistant Strains

ABSTRACT Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed. Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities againstCandida albicans and Cryptococcus neoformans. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against C. albicans was 0.39 μg/ml, and it was the most potent compound against C. neoformans (MIC, ≤0.09 μg/ml). Selected compounds were also found to be active againstAspergillus fumigatus, Fusarium solani,Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents.

scholarly journals Effects of Azole Antifungal Drugs on the Transition from Yeast Cells to Hyphae in Susceptible and Resistant Isolates of the Pathogenic Yeast Candida albicans

1999 ◽  
Vol 43 (4) ◽  
pp. 763-768 ◽  
Author(s):  
Kien C. Ha ◽  
Theodore C. White
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Molecular Mechanisms ◽  
Opportunistic Infections ◽  
Antifungal Drugs ◽  
Yeast Cells ◽  
Pathogenic Yeast ◽  
Oral Infections ◽  
Antifungal Drug Resistance ◽  
Hyphal Formation

ABSTRACT Oral infections caused by the yeast Candida albicansare some of the most frequent and earliest opportunistic infections in human immunodeficiency virus-infected patients. The widespread use of azole antifungal drugs has led to the development of drug resistance, creating a major problem in the treatment of yeast infections in AIDS patients and other immunocompromised individuals. Several molecular mechanisms that contribute to drug resistance have been identified. InC. albicans, the ability to morphologically switch from yeast cells (blastospores) to filamentous forms (hyphae) is an important virulence factor which contributes to the dissemination ofCandida in host tissues and which promotes infection and invasion. A positive correlation between the level of antifungal drug resistance and the ability to form hyphae in the presence of azole drugs has been identified. Under hypha-inducing conditions in the presence of an azole drug, resistant clinical isolates form hyphae, while susceptible yeast isolates do not. This correlation is observed in a random sample from a population of susceptible and resistant isolates and is independent of the mechanisms of resistance.35S-methionine incorporation suggests that growth inhibition is not sufficient to explain the inhibition of hyphal formation, but it may contribute to this inhibition.

scholarly journals Efficacy of Polymer-Based Nanocarriers for Co-Delivery of Curcumin and Selected Anticancer Drugs

Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1556 ◽  
Author(s):  
Sibusiso Alven ◽  
Blessing Atim Aderibigbe
Keyword(s):  
Drug Resistance ◽  
Combination Therapy ◽  
Anticancer Drugs ◽  
Water Solubility ◽  
Review Article ◽  
High Rate ◽  
Therapeutic Outcomes ◽  
Biological Outcomes

Cancer remains a heavy health burden resulting in a high rate of mortality around the world. The presently used anticancer drugs suffer from several shortcomings, such as drug toxicity, poor biodegradability and bioavailability, and poor water solubility and drug resistance. Cancer is treated effectively by combination therapy whereby two or more anticancer drugs are employed. Most of the combination chemotherapies result in a synergistic effect and overcome drug resistance. Furthermore, the design of polymer-based nanocarriers for combination therapy has been reported by several researchers to result in promising therapeutic outcomes in cancer treatment. Curcumin exhibits good anticancer activity but its poor bioavailability has resulted in its incorporation into several polymer-based nanocarriers resulting in good biological outcomes. Furthermore, the incorporation of curcumin together with other anticancer drugs have been reported to result in excellent therapeutic outcomes in vivo and in vitro. Due to the potential of polymer-based nanocarriers, this review article will be focused on the design of polymer-based nanocarriers loaded with curcumin together with other anticancer drugs.

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