Potential of Nanoparticles in Combating Candida Infections

2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani
Keyword(s):  
Targeted Delivery ◽  
Recent Progress ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Fold Increase ◽  
Antifungal Drugs ◽  
Low Toxicity ◽  
Candida Infections ◽  
Made In

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.

scholarly journals Acylhydrazones as Antifungal Agents Targeting the Synthesis of Fungal Sphingolipids

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Cristina Lazzarini ◽  
Krupanandan Haranahalli ◽  
Robert Rieger ◽  
Hari Krishna Ananthula ◽  
Pankaj B. Desai ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Fungal Resistance ◽  
Content Type ◽  
Highly Active ◽  
Pharmacokinetic Properties ◽  
Pass Through

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.

Identification of a novel antifungal backbone of naphthalimide thiazoles with synergistic potential for chemical and dynamic treatment

2021 ◽  
Author(s):  
Peng-Li Zhang ◽  
Gopala Lavanya ◽  
Yang Yu ◽  
Bo Fang ◽  
Cheng-He Zhou
Keyword(s):  
Antioxidant Defense ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antioxidant Defense System ◽  
Antifungal Drugs ◽  
Defense System ◽  
High Incidence ◽  
Dynamic Treatment ◽  
Low Toxicity ◽  
Treatment Window

Aim: The high incidence and prevalence of fungal infections call for new antifungal drugs. This work was to develop naphthalimide thiazoles as potential antifungal agents. Results & methodology: These compounds showed significant antifungal potency toward some tested fungi. Especially, naphthalimide thiazole 4h with excellent anti- Candida tropicalis efficacy possessed good hemolysis level, low toxicity and no obvious resistance. Deciphering the mechanism showed that 4h interacted with DNA and disrupted the antioxidant defense system of C. tropicalis. Compound 4h also triggered membrane depolarization, leakage of cytoplasmic contents and LDH inhibition. Simultaneously, 4h rendered metabolic inactivation and eradicated the formed biofilms of C. tropicalis. Conclusion: The multifaceted synergistic effect initiated by naphthalimide thiazoles is a reasonable treatment window for prospective development.

scholarly journals CandidaBloodstream Infections in Italy: Changing Epidemiology during 16 Years of Surveillance

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Giuseppina Caggiano ◽  
Caterina Coretti ◽  
Nicola Bartolomeo ◽  
Grazia Lovero ◽  
Osvalda De Giglio ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Bloodstream Infections ◽  
Incidence Rates ◽  
Antifungal Drugs ◽  
Patient Groups ◽  
Almost All ◽  
Made In ◽  
Overall Mortality

Although considerable progress has been made in the management of patients with invasive fungal infections,Candidabloodstream infections are still widespread in hospital settings. Incidence rates vary geographically, often because of different patient populations. The aim of the present study was to describe the epidemiology of candidemia, to analyze the trend of species distribution, and to measure thein vitrosusceptibility to antifungal drugs in a university Italian hospital from 1998 to 2013. The antifungal susceptibility for allCandidaisolates was evaluated by broth microdilution assay (CLSI M27-A3 document). Of 394 episodes of candidemia, the average incidence was 3.06/10 000 admissions.C. albicansand non-albicans Candidaspecies caused 44.2% and 55.8% of the episodes, respectively.C. parapsilosis(62.2%) was the most common non-albicans.  C. albicanspredominated in almost all departments whereasC. parapsilosiswas found in adult and paediatric oncohaematology units (34.8% and 77.6%, resp.). Overall, mortality occurred in 111 (28.2%) patients. Death occurred most often in intensive care units (47.1%) and specialist surgeries (43.7%). Most of the isolates were susceptible to antifungal drugs, but there was an upward trend for azole (P<0.05). In conclusion, this study emphasizes the importance of monitoring local epidemiologic data and the diversity of patient groups affected.

In vitro antifungal and fungicidal activities and erythrocyte toxicities of cyclic lipodepsinonapeptides produced by Pseudomonas syringae pv. syringae.

1996 ◽  
Vol 40 (12) ◽  
pp. 2710-2713 ◽  
Author(s):  
K N Sorensen ◽  
K H Kim ◽  
J Y Takemoto
Keyword(s):  
Pseudomonas Syringae ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Fungal Resistance ◽  
Broth Microdilution ◽  
Antifungal Activities ◽  
Syringomycin E ◽  
Lead Compounds

Recent increases in fungal infections, the few available antifungal drugs, and increasing fungal resistance to the available antifungal drugs have resulted in a broadening of the search for new antifungal agents. Strains of Pseudomonas syringae pv. syringae produce cyclic lipodepsinonapeptides with antifungal activity. The in vitro antifungal and fungicidal activities of three cyclic lipodepsinonapeptides (syringomycin E, syringotoxin B, and syringostatin A) against medically important isolates were evaluated by a standard broth microdilution susceptibility method. Erythrocyte toxicities were also evaluated. All three compounds showed broad antifungal activities and fungicidal actions against most of the fungi tested. Overall, the cyclic lipodepsinonapeptides were more effective against yeasts than against the filamentous fungi. Syringomycin E and syringostatin A had very similar antifungal activities (2.5 to > 40 micrograms/ml) and erythrocyte toxicities. Syringotoxin B was generally less active (0.8 to 200 micrograms/ml) than syringomycin E and syringostatin A against most fungi and was less toxic to erythrocytes. With opportunities for modification, these compounds are potential lead compounds for improved antifungal agents.

scholarly journals Carveoylphenols and Their Antifungal Potential against Pathogenic Yeasts

Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 185 ◽  
Author(s):  
Iván Montenegro ◽  
Marco Mellado ◽  
Alessandra Russo ◽  
Bastian Said ◽  
Ximena Besoain ◽  
...  
Keyword(s):  
Spectroscopic Analysis ◽  
Fungal Infections ◽  
Biological Activities ◽  
Antifungal Drugs ◽  
Pathogenic Yeast ◽  
Structure Activity ◽  
Antifungal Potential ◽  
Preliminary Study ◽  
Candida Infections

Candida is a genus of yeasts and is the most common cause of fungal infections worldwide. However, only a few antifungal drugs are currently available for the treatment of Candida infections. In the last decade, terpenophenols have attracted much attention because they often possess a variety of biological activities. In the search for new antifungals, eight carveoylphenols were synthesized and characterized by spectroscopic analysis. By using the broth microdilution assay, the compounds were evaluated for antifungal activities in vitro against four human pathogenic yeast, and structure–activity relationships (SAR) were derived. Noteworthy, in this preliminary study, compounds 5 and 6, have shown a significant reduction in the growth of all Candida strains tested. Starting from these preliminary results, we have designed the second generation of analogous in this class, and further studies are in progress in our laboratories.

scholarly journals In vitro activity of four triazole antifungal drugs against clinically common and uncommon yeast species

2019 ◽  
Author(s):  
Narges Aslani ◽  
Tahereh Shokohi ◽  
Mohammad Reza Ataollahi ◽  
Saham Ansari ◽  
Yousef Gholampour ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Yeast Species ◽  
Fungal Infections ◽  
Geometric Mean ◽  
Antifungal Susceptibility ◽  
Active Agent ◽  
Antifungal Drugs ◽  
Selection Of

Background and Purpose: Incidence of fungal infections caused by opportunistic fungal pathogens, such as yeasts and yeast-like species, has undergone an increase in otherwise healthy individuals. These pathogens account for high mortality and show reduced susceptibility to the routine antifungal drugs. Accordingly, antifungal susceptibility testing is an urgent need in the determination of the susceptibility spectrum of antifungals and selection of appropriate antifungal agents for the management of patients with fungal infection.Materials and Methods: The present study was conducted on 110 yeast strains belonging to 15 species recovered from clinical specimens. Susceptibility of the isolates to four antifungal drugs (i.e., fluconazole, itraconazole, voriconazole, and posaconazole) was tested according to the Clinical and Laboratory Standards Institute guidelines M27-A3 and M27-S4.Results: Fluconazole exhibited no activity against 4.3% (n=2) of C. albicans isolates, whereas the remaining 44 isolates had a minimum inhibitory concentration (MIC) range of 0.125-4 μg/ml. Voriconazole had the lowest geometric mean MIC (0.03 μg/ml) against all isolated yeast species, followed by posaconazole (0.07 μg/ml), itraconazole (0.10 μg/ml), and fluconazole (0.60 μg/ml). Overall, all of the isolates had reduced voriconazole MICs with a MIC range of 0.016-0.5 μg/ml, except for one isolate of C. albicans that had a MIC of 1 μg/ml. Candida haemulonii as a multidrug-resistant fungus showed a fluconazole MIC of > 64 μg/ml.Conclusion: The current study provides insight into the antifungal susceptibility profiles of clinically common and uncommon yeast species to four triazole antifungal agents. According to our findings, voriconazole was the most active agent. Awareness about antifungal susceptibility patterns is highly helpful in the selection of appropriate antifungal drugs and identification of the efficiency of the currently used agents.

scholarly journals Spectrum and theIn VitroAntifungal Susceptibility Pattern of Yeast Isolates in Ethiopian HIV Patients with Oropharyngeal Candidiasis

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Birhan Moges ◽  
Adane Bitew ◽  
Aster Shewaamare
Keyword(s):  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Antifungal Drugs ◽  
Assay Method ◽  
Cryptococcus Laurentii ◽  
Susceptibility Pattern ◽  
Test Procedures ◽  
Disk Diffusion Assay ◽  
Diffusion Assay

Background.In Ethiopia, little is known regarding the distribution and thein vitroantifungal susceptibility profile of yeasts.Objective.This study was undertaken to determine the spectrum and thein vitroantifungal susceptibility pattern of yeasts isolated from HIV infected patients with OPC.Method.Oral pharyngeal swabs taken from oral lesions of study subjects were inoculated onto Sabouraud Dextrose Agar. Yeasts were identified by employing conventional test procedures and the susceptibility of yeasts to antifungal agents was evaluated by disk diffusion assay method.Result.One hundred and fifty-five yeast isolates were recovered of which 91 isolates were from patients that were not under HAART and 64 were from patients that were under HAART.C. albicanswas the most frequently isolated species followed byC. glabrata, C. tropicalis, C. krusei, C. kefyr, Cryptococcus laurentii, and Rhodotorulaspecies. Irrespective of yeasts isolated and identified, 5.8%, 5.8%, 12.3%, 8.4%, 0.6%, and 1.3% of the isolates were resistant to amphotericin B, clotrimazole, fluconazole, ketoconazole, miconazole, and nystatin, respectively.Conclusion.Yeast colonization rate of 69.2% and 31% resistance to six antifungal agents was documented. These highlight the need for nationwide study on the epidemiology of OPC and resistance to antifungal drugs.

scholarly journals Albumin Enhances Caspofungin Activity against Aspergillus Species by Facilitating Drug Delivery to Germinating Hyphae

2015 ◽  
Vol 60 (3) ◽  
pp. 1226-1233 ◽  
Author(s):  
Petros Ioannou ◽  
Aggeliki Andrianaki ◽  
Tonia Akoumianaki ◽  
Irene Kyrmizi ◽  
Nathaniel Albert ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cell Culture ◽  
Antifungal Agents ◽  
Fold Increase ◽  
Culture Conditions ◽  
The Other ◽  
Related Factors ◽  
Content Type

The modestin vitroactivity of echinocandins againstAspergillusimplies that host-related factors augment the action of these antifungal agentsin vivo. We found that, in contrast to the other antifungal agents (voriconazole, amphotericin B) tested, caspofungin exhibited a profound increase in activity against variousAspergillusspecies under conditions of cell culture growth, as evidenced by a ≥4-fold decrease in minimum effective concentrations (MECs) (P= 0. 0005). Importantly, the enhanced activity of caspofungin againstAspergillusspp. under cell culture conditions was strictly dependent on serum albumin and was not observed with the other two echinocandins, micafungin and anidulafungin. Of interest, fluorescently labeled albumin bound preferentially on the surface of germinatingAspergillushyphae, and this interaction was further enhanced upon treatment with caspofungin. In addition, supplementation of cell culture medium with albumin resulted in a significant, 5-fold increase in association of fluorescently labeled caspofungin withAspergillushyphae (P< 0.0001). Collectively, we found a novel synergistic interaction between albumin and caspofungin, with albumin acting as a potential carrier molecule to facilitate antifungal drug delivery toAspergillushyphae.

scholarly journals Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1059
Author(s):  
Saif Ahmad Khan ◽  
Saleha Rehman ◽  
Bushra Nabi ◽  
Ashif Iqubal ◽  
Nida Nehal ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Fold Increase ◽  
Pharmacokinetic Studies ◽  
Nanostructured Lipid Carrier ◽  
Brain Delivery ◽  
The Brain

Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential approach for overcoming the limited ATZ brain delivery. Methods: ATZ-loaded NLC was formulated using the quality by design-enabled approach and further optimized by employing the Box–Behnken design. The optimized nanoformulation was then characterized for several in vitro and in vivo assessments. Results: The optimized NLC showed small particle size of 227.6 ± 5.4 nm, high entrapment efficiency (71.09% ± 5.84%) and high drug loading capacity (8.12% ± 2.7%). The release pattern was observed to be biphasic exhibiting fast release (60%) during the initial 2 h, then trailed by the sustained release. ATZ-NLC demonstrated a 2.36-fold increase in the cumulative drug permeated across the rat intestine as compared to suspension. Pharmacokinetic studies revealed 2.75-folds greater Cmax in the brain and 4-fold improvement in brain bioavailability signifying the superiority of NLC formulation over drug suspension. Conclusion: Thus, NLC could be a promising avenue for encapsulating hydrophobic drugs and delivering it to their target site. The results suggested that increase in bioavailability and brain-targeted delivery by NLC, in all plausibility, help in improving the therapeutic prospects of atazanavir.

scholarly journals Current and Emerging Azole Antifungal Agents

1999 ◽  
Vol 12 (1) ◽  
pp. 40-79 ◽  
Author(s):  
Daniel J. Sheehan ◽  
Christopher A. Hitchcock ◽  
Carol M. Sibley
Keyword(s):  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Mechanisms Of Action ◽  
Current Status ◽  
In Vitro Susceptibility ◽  
Clinical Resistance ◽  
In Vitro Susceptibility Testing

SUMMARY Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole and itraconazole have proved to be safer than both amphotericin B and ketoconazole. Despite these advances, serious fungal infections remain difficult to treat, and resistance to the available drugs is emerging. This review describes present and future uses of the currently available azole antifungal agents in the treatment of systemic and superficial fungal infections and provides a brief overview of the current status of in vitro susceptibility testing and the growing problem of clinical resistance to the azoles. Use of the currently available azoles in combination with other antifungal agents with different mechanisms of action is likely to provide enhanced efficacy. Detailed information on some of the second-generation triazoles being developed to provide extended coverage of opportunistic, endemic, and emerging fungal pathogens, as well as those in which resistance to older agents is becoming problematic, is provided.

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