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Materials (Basel, Switzerland) May 2023Oral candidiasis is an opportunistic infection that affects mainly individuals with weakened immune system. Devices used in the oral area to treat this condition include...
Oral candidiasis is an opportunistic infection that affects mainly individuals with weakened immune system. Devices used in the oral area to treat this condition include buccal films, which present advantages over both oral tablets and gels. Since candidiasis causes pain, burning, and itching, the purpose of this work was to develop buccal films loaded with both lidocaine (anesthetic) and miconazole nitrate (MN, antifungal) to treat this pathology topically. MN was loaded in microparticles based on different natural polymers, and then, these microparticles were loaded in hydroxypropyl methylcellulose-gelatin-based films containing lidocaine. All developed films showed adequate adhesiveness and thickness. DSC and XRD tests suggested that the drugs were in an amorphous state in the therapeutic systems. Microparticles based on chitosan-alginate showed the highest MN encapsulation. Among the films, those containing the mentioned microparticles presented the highest tensile strength and the lowest elongation at break, possibly due to the strong interactions between both polymers. These films allowed a fast release of lidocaine and a controlled release of MN. Due to the latter, these systems showed antifungal activity for 24 h. Therefore, the treatment of oropharyngeal candidiasis with these films could reduce the number of daily applications with respect to conventional treatments.
PubMed: 37176470
DOI: 10.3390/ma16093586 -
Photochemistry and Photobiology 2012Cutaneous and mucocutaneous Candida infections are considered to be important targets for antimicrobial photodynamic therapy (PDT). Clinical application of antimicrobial...
Cutaneous and mucocutaneous Candida infections are considered to be important targets for antimicrobial photodynamic therapy (PDT). Clinical application of antimicrobial PDT will require strategies that enhance microbial killing while minimizing damage to host tissue. Increasing the sensitivity of infectious agents to PDT will help achieve this goal. Our previous studies demonstrated that raising the level of oxidative stress in Candida by interfering with fungal respiration increased the efficiency of PDT. Therefore, we sought to identify compounds in clinical use that would augment the oxidative stress caused by PDT by contributing to reactive oxygen species (ROS) formation themselves. Based on the ability of the antifungal miconazole to induce ROS in Candida, we tested several azole antifungals for their ability to augment PDT in vitro. Although miconazole and ketoconazole both stimulated ROS production in Candida albicans, only miconazole enhanced the killing of C. albicans and induced prolonged fungistasis in organisms that survived PDT using the porphyrin TMP-1363 and the phenothiazine methylene blue as photosensitizers. The data suggest that miconazole could be used to increase the efficacy of PDT against C. albicans, and its mechanism of action is likely to be multifactorial.
Topics: Antifungal Agents; Candida albicans; Fluconazole; Miconazole; Microbial Sensitivity Tests; Oxidative Stress; Photochemotherapy; Photosensitizing Agents; Porphyrins; Reactive Oxygen Species
PubMed: 22077904
DOI: 10.1111/j.1751-1097.2011.01039.x -
Parasites & Vectors Mar 2016Imipramine, a tricyclic antidepressant widely used clinically, has other pharmacological effects, such as antileishmanial activity. Tricyclic antidepressants interact...
BACKGROUND
Imipramine, a tricyclic antidepressant widely used clinically, has other pharmacological effects, such as antileishmanial activity. Tricyclic antidepressants interact with lipid bilayers, and some studies have shown that imipramine inhibits methyltransferases. Leishmania spp. produces compounds with an ergostane skeleton instead of a cholesterol skeleton, and the inhibition of enzymes of the sterol biosynthesis pathway is an interesting therapeutic target. Among these enzymes, C-24 methyltransferase has been suggested to play an essential role, as its inhibition kills the parasites. In this context, we investigated whether imipramine alters the biosynthesis of sterols in L. amazonensis and evaluated the efficacy of imipramine alone and in combination with miconazole, a classical inhibitor of another step in this pathway.
METHODS
To analyze the interference of imipramine with sterol metabolism, promastigotes of L. amazonensis were cultured with medium alone, 15 or 30 μM imipramine or 4 μM miconazole, and their lipids were extracted with methanol/chloroform/water (1:0.5:0.4 v/v) and analyzed by GC/MS. To assess the antileishmanial activity of the treatments, promastigotes of L. amazonensis were incubated with various concentrations of imipramine up to 100 μM and up to 24 μM miconazole. Promastigotes were also treated with the combination of imipramine and miconazole at concentrations up to 12.5 μM of imipramine and 24 μM of miconazole. Parasite growth was evaluated by the MTT assay. The fractional inhibitory concentration index (FICI) was calculated to determine whether there were synergistic effects. Peritoneal macrophages with and without L. amazonensis infection were treated with miconazole (0 - 16 μM) or imipramine (0 to 50 μM) for 72 hours. For assays of the combined treatment in amastigotes, the concentration of imipramine was fixed at 12.5 μM and various concentrations of miconazole were used up to 16 μM. The infection rate was determined by counting the infected macrophages under a light microscope.
FINDINGS
Promastigotes treated with imipramine accumulated cholesta-5,7,22-trien-3β-ol and cholesta-7-24-dien- 3β-ol, sterols that normally increase after treatment with classical inhibitors of C-24 methyltransferase. The IC50 of miconazole in promastigotes decreased when it was used in combination with imipramine, resulting in an additive effect, with a FICI value of 0.83. Imipramine also showed activity against intracellular amastigotes and enhanced the activity of miconazole, without apparent toxicity to the host cells.
CONCLUSIONS
Imipramine was confirmed to have antileishmanial activity in both forms of the parasite, affecting the sterol biosynthesis of the organisms. Using imipramine in combination with azoles may be advantageous for the treatment of leishmaniasis.
Topics: Animals; Antiprotozoal Agents; Cell Survival; Drug Synergism; Formazans; Gas Chromatography-Mass Spectrometry; Imipramine; Leishmania mexicana; Macrophages, Peritoneal; Mice; Miconazole; Parasitic Sensitivity Tests; Sterols; Tetrazolium Salts; Thiazoles
PubMed: 27036654
DOI: 10.1186/s13071-016-1467-8 -
PloS One 2016Oral candidiasis (OC) is a common oral fungal infection. Recently, miconazole mucoadhesive tablets have been gaining attention for OC treatment. Despite trials in... (Randomized Controlled Trial)
Randomized Controlled Trial
The Efficacy and Safety of Miconazole Nitrate Mucoadhesive Tablets versus Itraconazole Capsules in the Treatment of Oral Candidiasis: An Open-Label, Randomized, Multicenter Trial.
BACKGROUND
Oral candidiasis (OC) is a common oral fungal infection. Recently, miconazole mucoadhesive tablets have been gaining attention for OC treatment. Despite trials in patients with human immunodeficiency virus and cancer, evidence of its application in the large-scale, general population with OC is lacking. This study aimed to evaluate the efficacy and safety of miconazole nitrate mucoadhesive tablets in comparison with itraconazole capsules for OC treatment.
METHODS
The study was a randomized, open-label, parallel-armed, multicenter clinical trial. Totally, 343 patients diagnosed with OC, who met the inclusion criteria, were randomly assigned to either a treatment group that received miconazole nitrate mucoadhesive tablets (10 mg) once daily or a control group that received itraconazole capsules (100 mg QD) for 2 weeks, and were followed up for 2 weeks. The clinical cure, improvement of clinical symptoms/signs, mycologic cure, and safety were evaluated.
RESULTS
The mucoadhesive tablets (n = 171) did not show inferiority to itraconazole (n = 172) in the treatment of OC. At the end of the 14-day treatment, the clinical cure rates were 45.29% and 41.76% in the miconazole and itraconazole groups, respectively (P = 0.3472). At the end of the 14-day follow-up, the clinical cure rates were 51.18% and 41.76% in the miconazole and itraconazole groups, respectively (P = 0.0329). Adverse events occurred in 53 subjects (33 in the miconazole group and 20 in the itraconazole group). There was no statistical difference in the safety profile between miconazole and itraconazole (P = 0.0533). Thrombocytopenic purpura, although rare, occurred in one patient in the miconazole group and was considered a drug-related, severe adverse event.
CONCLUSION
Miconazole nitrate mucoadhesive tablets may be as effective as systemic itraconazole capsule for OC treatment. Physicians should be cautious about thrombocytopenic purpura occurring as a rare and serious adverse event of miconazole nitrate.
TRIAL REGISTRATION
Chinese Clinical Trial Register ChiCTR-TRC-13003935.
Topics: Adult; Antifungal Agents; Candidiasis, Oral; Capsules; Female; Humans; Itraconazole; Male; Miconazole; Middle Aged; Tablets
PubMed: 27977721
DOI: 10.1371/journal.pone.0167880 -
Antimicrobial Agents and Chemotherapy Sep 2020The occurrence and recurrence of mucosal biofilm-related infections, such as oral and vulvovaginal candidiasis, are serious clinical issues. Vaginal infections caused...
The occurrence and recurrence of mucosal biofilm-related infections, such as oral and vulvovaginal candidiasis, are serious clinical issues. Vaginal infections caused by spp., for example, affect 70 to 75% of women at least once during their lives. Miconazole (MCZ) is the preferred topical treatment against these fungal infections, yet it has only moderate antibiofilm activity. Through screening of a drug-repurposing library, we identified the quaternary ammonium compound domiphen bromide (DB) as an MCZ potentiator against biofilms. DB displayed synergistic anti- biofilm activity with MCZ, reducing the number of viable biofilm cells 1,000-fold. In addition, the MCZ-DB combination also resulted in significant killing of biofilm cells of azole-resistant , , and isolates. , the MCZ-DB combination had significantly improved activity in a vulvovaginal candidiasis rat model compared to that of single-compound treatments. Data from an artificial evolution experiment indicated that the development of resistance against the combination did not occur, highlighting the potential of MCZ-DB combination therapy to treat biofilm-related infections.
Topics: Animals; Antifungal Agents; Biofilms; Candida; Candida albicans; Female; Humans; Miconazole; Microbial Sensitivity Tests; Quaternary Ammonium Compounds; Rats
PubMed: 32690639
DOI: 10.1128/AAC.01296-20 -
The Cochrane Database of Systematic... Oct 2015Invasive fungal infection is an important cause of mortality and morbidity in very preterm or very low birth weight infants. Uncertainty exists about the effect of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Invasive fungal infection is an important cause of mortality and morbidity in very preterm or very low birth weight infants. Uncertainty exists about the effect of prophylactic oral/topical non-absorbed antifungals to reduce mucocutaneous colonisation and so limit the risk of invasive fungal infection in this population.
OBJECTIVES
To assess the effect of prophylactic oral/topical non-absorbed antifungal therapy on the incidence of invasive fungal infection, mortality and morbidity in very preterm or very low birth weight infants.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL: The Cochrane Library, 2015, Issue 7), MEDLINE, EMBASE, and CINAHL (to May 2015), conference proceedings, and previous reviews.
SELECTION CRITERIA
Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic oral/topical non-absorbed antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very preterm or very low birth weight infants.
DATA COLLECTION AND ANALYSIS
We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors.
MAIN RESULTS
Four trials, in which a total of 1800 infants participated, compared oral/topical non-absorbed antifungal prophylaxis (nystatin or miconazole) with placebo or no drug. These trials had various methodological weaknesses including quasi-randomisation, lack of allocation concealment, and lack of blinding of intervention and outcomes assessment. The incidence of invasive fungal infection was very high in the control groups of three of these trials. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection (typical risk ratio 0.20, 95% confidence interval 0.14 to 0.27; risk difference -0.18, -0.21 to -0.15) but substantial statistical heterogeneity was present. We did not find a statistically significant effect on mortality (typical risk ratio 0.87, 0.72 to 1.05; risk difference -0.03, -0.06 to 0.01). None of the trials assessed posthospital discharge outcomes. Three trials (N = 326) assessed the effect of oral/topical non-absorbed versus systemic antifungal prophylaxis. Meta-analyses did not find any statistically significant differences in the incidences of invasive fungal infection or all-cause mortality.
AUTHORS' CONCLUSIONS
The finding of a reduction in risk of invasive fungal infection in very low birth weight infants treated with oral/topical non-absorbed antifungal prophylaxis should be interpreted cautiously because of methodological weaknesses in the included trials. Further large randomised controlled trials in current neonatal practice settings are needed to resolve this uncertainty. These trials might compare oral/topical non-absorbed antifungal agents with placebo, with each other, or with systemic antifungal agents and should include an assessment of effect on long-term neurodevelopmental outcomes.
Topics: Administration, Oral; Administration, Topical; Antifungal Agents; Fluconazole; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Miconazole; Mycoses; Nystatin; Randomized Controlled Trials as Topic
PubMed: 26497202
DOI: 10.1002/14651858.CD003478.pub5 -
British Journal of Clinical Pharmacology Oct 2004The aim of this study was to compare salivary miconazole pharmacokinetics following once daily application of bioadhesive tablets (50 or 100 mg), vs the current... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
AIMS
The aim of this study was to compare salivary miconazole pharmacokinetics following once daily application of bioadhesive tablets (50 or 100 mg), vs the current treatment with a gel (3 times a day, 375 mg day(-1)).
METHODS
A three way cross over study was carried out in 18 healthy subjects (nine males, nine females) with a 1 week washout period between each treatment. Plasma and salivary pharmacokinetics of miconazole were assessed over a 24-h period.
RESULTS
In all subjects the tablets gave higher and more prolonged salivary miconazole concentrations than the gel. Thus salivary miconazole AUC(0,24 h) was 37.2 times greater for the 100 mg tablet (90% confidence interval [CI] 22.9, 60.5) and 18.9 times greater for the 50 mg tablet (CI 11.7, 30.6) compared with the gel. Similarly, Cmax was 17.2 times greater (CI 11.8, 25.2) and 7.8 times greater (CI 5.3, 11.4) for the 100 mg tablet and 50 mg tablet, respectively. Comparison of the 100 mg and 50 mg tablets gave ratios of 2.2 and 2.0 for Cmax and AUC(0,24 h), respectively (CI 1.5, 3.2 and 1.2, 3.2). The mean time that salivary miconazole concentrations were above 0.4 micro g ml(-1) (the concentration reached 3 h after application of the oral gel according to published data) or above 1.0 microg ml(-1) (the MIC of some Candida species) was greater for both bioadhesive tablets than for the oral gel (10-14 h vs 1.5 h and 7 h vs 0.6 h). Only 19 plasma samples from eight subjects had concentrations of miconazole above 0.4 micro g ml(-1). Ten of these were taken from five subjects after administration of the gel and nine from three subjects after administration of the tablets.
CONCLUSIONS
These data strongly support the further development of miconazole bioadhesive tablets as a sustained release formulation leading to improved antifungal exposure in the buccal cavity. A single daily application should improve compliance, whereas the low systemic absorption of miconazole will alleviate concerns regarding drug interactions and adverse effects.
Topics: Administration, Oral; Adult; Antifungal Agents; Cross-Over Studies; Delayed-Action Preparations; Female; Gels; Humans; Male; Miconazole; Plasma; Saliva; Tablets
PubMed: 15373926
DOI: 10.1111/j.1365-2125.2004.02154.x -
Drug Delivery Dec 2022Nanocapsules can be equated to other nanovesicular systems in which a drug is entrapped in a void containing liquid core surrounded by a coat. The objective of the...
Nanocapsules can be equated to other nanovesicular systems in which a drug is entrapped in a void containing liquid core surrounded by a coat. The objective of the present study was to investigate the potential of polymeric and lipid nanocapsules (LNCs) as innovative carrier systems for miconazole nitrate (MN) topical delivery. Polymeric nanocapsules and LNCs were prepared using emulsification/nanoprecipitation technique where the effect of poly(ε-caprolactone (PCL) and lipid matrix concentrations with respect to MN were assessed. The resulted nanocapsules were examined for their average particle size, zeta potential, %EE, and drug release. Optimum formulation in both polymeric and lipidic nanocapsules was further subjected to anti-fungal activity and permeation tests. Based on the previous results, nanoencapsulation strategy into polymeric and LNCs created formulations of MN with slow biphasic release, high %EE, and improved stability, representing a good approach for the delivery of MN. PNCs were best fitted to Higuchi's diffusion while LNCs followed Baker and Lonsdale model in release kinetics. The encapsulated MN either in PNCs or LNCs showed higher cell viability in WISH amniotic cells in comparison with free MN. PNCs showed less permeation. PNCs were accompanied by high stability and more amount drug deposition (32.2 ± 3.52 µg/cm) than LNCs (12.7 ± 1.52 µg/cm). The antifungal activity of the PNCs was high 19.07 mm compared to 11.4 mm for LNCs. In conclusion, PNCs may have an advantage over LNCs by offering dual action for both superficial and deep fungal infections.
Topics: Administration, Cutaneous; Animals; Antifungal Agents; Cell Line; Cell Survival; Chemistry, Pharmaceutical; Drug Carriers; Drug Liberation; Drug Stability; Humans; Lipids; Male; Miconazole; Nanocapsules; Nanoparticle Drug Delivery System; Particle Size; Polyesters; Rats; Rats, Sprague-Dawley; Surface Properties
PubMed: 35037528
DOI: 10.1080/10717544.2022.2026535 -
Nutrition Research and Practice Dec 2015Reactive oxygen species (ROS) formation is closely related to miconazole-induced heart dysfunction. Although rhamnetin has antioxidant effects, it remained unknown...
BACKGROUND/OBJECTIVES
Reactive oxygen species (ROS) formation is closely related to miconazole-induced heart dysfunction. Although rhamnetin has antioxidant effects, it remained unknown whether it can protect against miconazole-induced cardiomyocyte apoptosis. Thus, we investigated the effects of rhamnetin on miconazole-stimulated H9c2 cell apoptosis.
MATERIALS/METHODS
Cell morphology was observed by inverted microscope and cell viability was determined using a WelCount™ cell proliferation assay kit. Miconazole-induced ROS production was evaluated by fluorescence-activated cell sorting with 6-carboxy-2',7'-dichlorofluoroscein diacetate (H2DCF-DA) stain. Immunoblot analysis was used to determine apurinic/apyrimidinic endonuclease 1 (APE/Ref-1) and cleaved cysteine-aspartic protease (caspase) 3 expression. NADPH oxidase levels were measured using real-time polymerase chain reaction.
RESULTS
Miconazole (3 and 10 µM) induced abnormal morphological changes and cell death in H9c2 cells. Rhamnetin enhanced the viability of miconazole (3 µM)-treated cells in a dose-dependent manner. Rhamnetin (1 and 3 µM) treatment downregulated cleaved caspase 3 and upregulated APE/Ref-1 expression in miconazole-stimulated cells. Additionally, rhamnetin significantly reduced ROS generation.
CONCLUSIONS
Our data suggest that rhamnetin may have cytoprotective effects in miconazole-stimulated H9c2 cardiomyocytes via ROS inhibition. This effect most likely occurs through the upregulation of APE/Ref-1 and attenuation of hydrogen peroxide levels.
PubMed: 26634046
DOI: 10.4162/nrp.2015.9.6.586 -
Drug Delivery Dec 2021Recurrent aphthous ulcer (RAU) is a well-known painful, inflammatory disease with uncertain etiology for which local symptomatic therapy is only available. The aim of...
Recurrent aphthous ulcer (RAU) is a well-known painful, inflammatory disease with uncertain etiology for which local symptomatic therapy is only available. The aim of this study was to formulate and characterize muco-adhesive sponges containing a mixture of tenoxicam and miconazole nitrate to manage pain, inflammation and avoid candida infection that may accompany RAU due to poor oral hygiene. Two polymers at different concentrations were used to prepare sponges applying simple freeze-drying. Medicated chitosan (2%) sponges (mC2) showed acceptable physical appearance, surface pH (6.3 ± 0.042), porosity (25.7% ± 1.8), swelling index (5.7 ± 0.11), and muco-adhesion time (115 min.±0.813 and 155 min.±1.537, respectively), muco-adhesion force (0.09 N ± 0.002) and scanning electron microscope (SEM) images. For concurrent clear-cut determination of tenoxicam and miconazole nitrate from mC2, a new UPLC method was developed and validated. mC2 sponges exhibited superior drug release profiles where ∼100% of tenoxicam released within 5 min for fast pain relief with a more prolonged miconazole nitrate release. Furthermore, animal study revealed that mC2 caused a significant decrease in the acetic acid-induced ulcer size in rats after 6 days of treatment ( < .0001) compared to negative and positive controls. Additionally, histopathological examination showed faster healing with complete restoration of the normal oral histology in rats. The present study concludes that chitosan sponge loaded with a combination of tenoxicam and miconazole nitrate could improve healing of RAU cases.
Topics: Adhesives; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Carboxymethylcellulose Sodium; Chitosan; Dose-Response Relationship, Drug; Drug Carriers; Drug Liberation; Freeze Drying; Hydrogen-Ion Concentration; Miconazole; Microscopy, Electron, Scanning; Piroxicam; Rats; Stomatitis, Aphthous; Wound Healing
PubMed: 33342321
DOI: 10.1080/10717544.2020.1858999