scholarly journals In Vitro and In Vivo Inhibitory Activity of Limonene against Different Isolates of Candida spp.

2020 ◽  
Vol 6 (3) ◽  
pp. 183
Author(s):  
Julián E. Muñoz ◽  
Diego C. P. Rossi ◽  
Daniela L. Jabes ◽  
David Aciole Barbosa ◽  
Fernanda F. M. Cunha ◽  
...  
Keyword(s):  
Protective Role ◽  
Infection Process ◽  
Antifungal Drugs ◽  
Candida Spp ◽  
Healthy Human ◽  
Fungal Burden ◽  
Fungal Damage ◽  
Therapeutic Alternatives

Commensal yeast from the genus Candida is part of the healthy human microbiota. In some cases, Candida spp. dysbiosis can result in candidiasis, the symptoms of which may vary from mild localized rashes to severe disseminated infections. The most prevalent treatments against candidiasis involve fluconazole, itraconazole, miconazole, and caspofungin. Moreover, amphotericin B associated with prolonged azole administration is utilized to control severe cases. Currently, numerous guidelines recommend echinocandins to treat invasive candidiasis. However, resistance to these antifungal drugs has increased dramatically over recent years. Considering this situation, new therapeutic alternatives should be studied to control candidiasis, which has become a major medical concern. Limonene belongs to the group of terpene molecules, known for their pharmacological properties. In this study, we evaluated in vitro the limonene concentration capable of inhibiting the growth of yeast from the genus Candida susceptible or resistant to antifungal drugs and its capacity to induce fungal damage. In addition, intravaginal fungal infection assays using a murine model infected by Candida albicans were carried out and the fungal burden, histopathology, and scanning electron microscopy were evaluated. All of our results suggest that limonene may play a protective role against the infection process by yeast from the genus Candida.

scholarly journals In Vitro and In Vivo Anti-Candida spp. Activity of Plant-Derived Products

Plants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 494 ◽  
Author(s):  
Reginaldo dos Santos Pedroso ◽  
Brenda Lorena Balbino ◽  
Géssica Andrade ◽  
Maria Cecilia Pereira Sacardo Dias ◽  
Tavane Aparecida Alvarenga ◽  
...  
Keyword(s):  
Essential Oil ◽  
Essential Oils ◽  
Gallic Acid ◽  
Antifungal Drugs ◽  
Citrus Limon ◽  
Cupressus Sempervirens ◽  
Candida Spp ◽  
Fungistatic Activity

Candidiasis therapy, especially for candidiasis caused by Candida non-albicans species, is limited by the relatively reduced number of antifungal drugs and the emergence of antifungal tolerance. This study evaluates the anticandidal activity of 41 plant-derived products against Candida species, in both planktonic and biofilm cells. This study also evaluates the toxicity and the therapeutic action of the most active compounds by using the Caenorhabditis elegans–Candida model. The planktonic cells were cultured with various concentrations of the tested agents. The Cupressus sempervirens, Citrus limon, and Litsea cubeba essential oils as well as gallic acid were the most active anticandidal compounds. Candida cell re-growth after treatment with these agents for 48 h demonstrated that the L. cubeba essential oil and gallic acid displayed fungistatic activity, whereas the C. limon and C. sempervirens essential oils exhibited fungicidal activity. The C. sempervirens essential oil was not toxic and increased the survival of C. elegans worms infected with C. glabrata or C. orthopsilosis. All the plant-derived products assayed at 250 µg/mL affected C. krusei biofilms. The tested plant-derived products proved to be potential therapeutic agents against Candida, especially Candida non-albicans species, and should be considered when developing new anticandidal agents.

scholarly journals DectiSomes: Glycan Targeting of Liposomal Drugs Improves the Treatment of Disseminated Candidiasis

2021 ◽  
Author(s):  
Suresh Ambati ◽  
Tuyetnhu Pham ◽  
Zachary A. Lewis ◽  
Xiaorong Lin ◽  
Richard B. Meagher
Keyword(s):  
Fungal Infections ◽  
Drug Efficacy ◽  
Antifungal Drugs ◽  
Outer Cell ◽  
Candida Spp ◽  
Fungal Burden ◽  
Disseminated Candidiasis ◽  
Binding Domains ◽  
One Year

Candida albicans causes life-threatening disseminated candidiasis. Individuals at greatest risk have weakened immune systems. An outer cell wall, exopolysaccharide matrix, and biofilm rich in oligoglucans and oligomannans help Candida spp. evade host defenses. Even after antifungal treatment, the one-year mortality rate exceeds 25%. Undoubtedly, there is room to improve drug performance. The mammalian C-type lectin pathogen receptors Dectin-1 and Dectin-2 bind to fungal oligoglucans and oligomannans, respectively. We previously coated amphotericin B-loaded liposomes, AmB-LLs, pegylated analogs of AmBisome, with the ligand binding domains of these two Dectins. DectiSomes, DEC1-AmB-LLs and DEC2-AmB-LLs, showed two distinct patterns of binding to the exopolysaccharide matrix surrounding C. albicans hyphae grown in vitro. Here we showed that DectiSomes were preferentially associated with fungal colonies in the kidneys. In a neutropenic mouse model of candidiasis, DEC1-AmB-LLs and DEC2-AmB-LLs delivering only one dose of 0.2 mg/kg AmB reduced the kidney fungal burden several fold relative to AmB-LLs. DEC1-AmB-LLs and DEC2-AmB-LLs increased the percent of surviving mice 2.5-fold and 8.3-fold, respectively, relative to AmB-LLs. Dectin-2 targeting of anidulafungin loaded liposomes, DEC2-AFG-LLs, and of commercial AmBisome, DEC2-AmBisome, reduced fungal burden in the kidneys several fold over their untargeted counterparts. The data herein suggest that targeting of a variety of antifungal drugs to fungal glycans may achieve lower safer effective doses and improve drug efficacy against a variety of invasive fungal infections.

scholarly journals Novel antifungal activity of Q-Griffithsin, a broad-spectrum antiviral lectin

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Henry Nabeta ◽  
Joseph C Kouokam ◽  
Amanda Lasnik ◽  
Joshua Fuqua ◽  
Kenneth E Palmer
Keyword(s):  
Cell Wall ◽  
Inhibitory Activity ◽  
Lectin Binding ◽  
Antifungal Drugs ◽  
Vaginal Candidiasis ◽  
Control Group ◽  
Fungal Burden ◽  
Growth Inhibitory Activity

Background There is a rising global trend in candida strains with high resistance to fluconazole and other antifungal drugs, hence the need for novel agents. Here, we investigated the anti-Candida activity of Q-Griffithsin (Q-GRFT), a lectin naturally produced by the red-sea algae, Griffithsia spp. Methods To assess in vitro growth inhibitory activity, C. albicans was incubated with Q-GRFT on agar plates and in broth media. We investigated GFP-bound Q-GRFT’s ability to adhere to C. albicans using fluorescence microscopy and fluorescence intensity assessments. To demonstrate in vivogrowth inhibitory activity, CBA/J mice were treated per vaginam with Q-GRFT followed by challenge with C. albicans, and fungal burden determined following vaginal lavage. Results Wild type fluorescently labeled Q-GRFT displayed higher fluorescence than the lectin-binding site deficient variant following incubation with C. albicans. Q-GRFT localized around the fungal cells and bound to α-mannan in the cell wall. Q-GRFT significantly inhibited C. albicans growth in broth and on agar plates, disrupted the integrity of the cell wall, and induced ROS formation. The lectin significantly inhibited the growth of C. glabrata, C. parapsilosis and C. krusei, with modest activity against C. auris CDC388 and C. auris CDC389 strains in vitro. Topical treatment resulted in a lower fungal burden compared to the vehicle control group in vaginal candidiasis. Conclusion Q-GRFT binds to and inhibits C. albicans growth both in vitro and in vivo. Further studies are needed to establish the mechanism of growth inhibition.

scholarly journals Ibrexafungerp: A First-in-Class Oral Triterpenoid Glucan Synthase Inhibitor

2021 ◽  
Vol 7 (3) ◽  
pp. 163 ◽  
Author(s):  
Sabelle Jallow ◽  
Nelesh P. Govender
Keyword(s):  
Pathogenic Fungi ◽  
Candida Spp ◽  
Fungal Cell ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Synthase Inhibitor ◽  
Increased Activity ◽  
In Vitro Data

Ibrexafungerp (formerly SCY-078 or MK-3118) is a first-in-class triterpenoid antifungal or “fungerp” that inhibits biosynthesis of β-(1,3)-D-glucan in the fungal cell wall, a mechanism of action similar to that of echinocandins. Distinguishing characteristics of ibrexafungerp include oral bioavailability, a favourable safety profile, few drug–drug interactions, good tissue penetration, increased activity at low pH and activity against multi-drug resistant isolates including C. auris and C. glabrata. In vitro data has demonstrated broad and potent activity against Candida and Aspergillus species. Importantly, ibrexafungerp also has potent activity against azole-resistant isolates, including biofilm-forming Candida spp., and echinocandin-resistant isolates. It also has activity against the asci form of Pneumocystis spp., and other pathogenic fungi including some non-Candida yeasts and non-Aspergillus moulds. In vivo data have shown IBX to be effective for treatment of candidiasis and aspergillosis. Ibrexafungerp is effective for the treatment of acute vulvovaginal candidiasis in completed phase 3 clinical trials.

scholarly journals The Novel Arylamidine T-2307 MaintainsIn VitroandIn VivoActivity against Echinocandin-Resistant Candida albicans

2014 ◽  
Vol 59 (2) ◽  
pp. 1341-1343 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Annette W. Fothergill ◽  
Rosie Bocanegra ◽  
Marcos Olivo ◽  
...  
Keyword(s):  
Body Weight ◽  
Candida Albicans ◽  
Invasive Candidiasis ◽  
Placebo Control ◽  
The Novel ◽  
Content Type ◽  
Fungal Burden ◽  
Potential Use

ABSTRACTWe evaluated thein vitroandin vivoactivities of the investigational arylamidine T-2307 against echinocandin-resistantCandida albicans. T-2307 demonstrated potentin vitroactivity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistantC. albicansinfections.

scholarly journals Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technology

2009 ◽  
Vol 59 (1) ◽  
pp. 15-30 ◽  
Author(s):  
Pramod Kumar ◽  
Sanjay Singh ◽  
Brahmeshwar Mishra
Keyword(s):  
Drug Release ◽  
Extended Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Tramadol Hydrochloride ◽  
Release Formulation ◽  
Extended Release Formulation

Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technologyExtended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media.In vivostudy was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax,tmax,AUC0-24,MRT) and relative bioavailability were calculated. Thein vitroandin vivoresults were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation.In vitro-in vivocorrelation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R= 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.

MyD88-Dependent Glucose Restriction and Itaconate Production Control Brucella Infection

2021 ◽  
Author(s):  
Carolyn A. Lacey ◽  
Bárbara Ponzilacqua-Silva ◽  
Catherine A. Chambers ◽  
Alexis S. Dadelahi ◽  
Jerod A. Skyberg
Keyword(s):  
Glucose Transporter ◽  
Production Control ◽  
Brucella Melitensis ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Ifn Γ ◽  
Glucose Restriction ◽  
Myd88 Signaling

Brucellosis is one of the most common global zoonoses and is caused by facultative intracellular bacteria of the genus Brucella . Numerous studies have found that MyD88 signaling contributes to protection against Brucella , however the underlying mechanism has not been entirely defined. Here we show that MyD88 signaling in hematopoietic cells contributes both to inflammation and to control of Brucella melitensis infection in vivo . While the protective role of MyD88 in Brucella infection has often been attributed to promotion of IFN-γ production, we found that MyD88 signaling restricts host colonization by B. melitensis even in the absence of IFN-γ. In vitro , we show that MyD88 promotes macrophage glycolysis in response to B. melitensis . Interestingly, a B. melitensis mutant lacking the glucose transporter, GluP, was more highly attenuated in MyD88 -/- than in WT mice, suggesting MyD88 deficiency results in an increased availability of glucose in vivo which Brucella can exploit via GluP. Metabolite profiling of macrophages identified several metabolites regulated by MyD88 in response to B. melitensis , including itaconate. Subsequently, we found that itaconate has antibacterial effects against Brucella and also regulates the production of pro-inflammatory cytokines in B. melitensis -infected macrophages. Mice lacking the ability to produce itaconate were also more susceptible to B. melitensis in vivo . Collectively, our findings indicate that MyD88-dependent changes in host metabolism contribute to control of Brucella infection.

scholarly journals Optimized Chitosan/Anion Polyelectrolyte Complex Based Inserts for Vaginal Delivery of Fluconazole: In Vitro/In Vivo Evaluation

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 227 ◽  
Author(s):  
Bayan Darwesh ◽  
Hibah Aldawsari ◽  
Shaimaa Badr-Eldin
Keyword(s):  
Vaginal Delivery ◽  
Polyelectrolyte Complex ◽  
Inflammatory Cells ◽  
Antifungal Drugs ◽  
Vaginal Candidiasis ◽  
Histological Evaluation ◽  
Anionic Polymer ◽  
In Vivo Evaluation

(1) Background: Fluconazole, used orally for vaginal candidiasis, has reported gastrointestinal side effects. Therefore, researchers directed towards the drug vaginal delivery. However, vaginal delivery is limited by poor retention and leakage. Thus, this work aimed at exploring chitosan/anion polyelectrolyte complex (PEC) for the formulation of fluconazole vaginal inserts with controlled release and appreciable mucoadhesion. (2) Methods: PECs were prepared and assessed for interactions. Fluconazole PEC based vaginal inserts were prepared by lyophilization using mannitol. 3151 factorial design was applied to investigate the effect of the anion type and Chitosan/anion ratio on the inserts mucoadhesion and release properties. The optimized insert [based on 5:5 chitosan: anionic polymer (sodium alginate)] release was modulated by the release retardant; Compritol® 888. The selected formulation was subjected to microbiological and histological evaluation. (3) Results: Fluconazole inserts showed satisfactory drug content, acceptable friability percentages and highest swelling indices at six hours. Statistical analysis showed significant effect of the studied factors on detachment force and release properties. Microbiological assays revealed significantly higher antifungal activity of inserts compared to fluconazole solution. Reduced inflammatory cells were confirmed by histological evaluation. (4) Conclusion: CH/Alg based vaginal insert could be a promising platform for vaginal delivery of antifungal drugs used for vaginal candidiasis treatment.

Cardiotoxicity and myocardial infarction-associated DNA damage induced by thiamethoxam in vitro and in vivo: Protective role ofTrigonella foenum-graecumseed-derived polysaccharide

2018 ◽  
Vol 34 (3) ◽  
pp. 271-282 ◽  
Author(s):  
Amal Feki ◽  
Hajer Ben Saad ◽  
Intidhar Bkhairia ◽  
Naourez Ktari ◽  
Manel Naifar ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Dna Damage ◽  
Protective Role

scholarly journals Reversal of Azole Resistance inCandida albicansby Sulfa Antibacterial Drugs

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Hassan E. Eldesouky ◽  
Abdelrahman Mayhoub ◽  
Tony R. Hazbun ◽  
Mohamed N. Seleem
Keyword(s):  
Treatment Options ◽  
Antifungal Drugs ◽  
Infection Model ◽  
Azole Resistance ◽  
Global Public Health ◽  
Sulfa Drugs ◽  
Antibacterial Drugs ◽  
Content Type

ABSTRACTInvasive candidiasis presents an emerging global public health challenge due to the emergence of resistance to the frontline treatment options, such as fluconazole. Hence, the identification of other compounds capable of pairing with fluconazole and averting azole resistance would potentially prolong the clinical utility of this important group. In an effort to repurpose drugs in the field of antifungal drug discovery, we explored sulfa antibacterial drugs for the purpose of reversing azole resistance inCandida. In this study, we assembled and investigated a library of 21 sulfa antibacterial drugs for their ability to restore fluconazole sensitivity inCandida albicans. Surprisingly, the majority of assayed sulfa drugs (15 of 21) were found to exhibit synergistic relationships with fluconazole by checkerboard assay with fractional inhibitory concentration index (ΣFIC) values ranging from <0.0312 to 0.25. Remarkably, five sulfa drugs were able to reverse azole resistance in a clinically achievable range. The structure-activity relationships (SARs) of the amino benzene sulfonamide scaffold as antifungal agents were studied. We also identified the possible mechanism of the synergistic interaction of sulfa antibacterial drugs with azole antifungal drugs. Furthermore, the ability of sulfa antibacterial drugs to inhibitCandidabiofilm by 40%in vitrowas confirmed. In addition, the effects of sulfa-fluconazole combinations onCandidagrowth kinetics and efflux machinery were explored. Finally, using aCaenorhabditis elegansinfection model, we demonstrated that the sulfa-fluconazole combination does possess potent antifungal activityin vivo, reducingCandidain infected worms by ∼50% compared to the control.

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