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BMC Oral Health Feb 2024Oral thrush is the most common occurring fungal infection in the oral cavity in uncontrolled diabetic patients, it is treated by various antifungal drugs according to... (Randomized Controlled Trial)
Randomized Controlled Trial
The anti-fungal effect of miconazole and miconazole-loaded chitosan nanoparticles gels in diabetic patients with Oral candidiasis-randomized control clinical trial and microbiological analysis.
BACKGROUND
Oral thrush is the most common occurring fungal infection in the oral cavity in uncontrolled diabetic patients, it is treated by various antifungal drugs according to each case. This study aimed to evaluate the therapeutic effects of topical application of miconazole and miconazole-loaded chitosan nanoparticles in treatment of diabetic patients with oral candidiasis.
METHODS
In this randomized controlled clinical trial. A total of 80 diabetic patients presenting with symptomatic oral candidiasis were randomly assigned into two treatment groups: miconazole and miconazole-loaded chitosan nanoparticles. The patients were treated for 28 days, and clinical assessments were conducted at baseline, 7, 14, 21 and 28 days. Clinical parameters, including signs and symptoms of oral candidiasis were evaluated and microbiological analysis was performed to determine the Candida species and assess their susceptibility to the antifungal agents. Statistical analysis was done to the categorical and numerical data using chi-square test and Kruskal Wallis test.
RESULTS
The antifungal efficacy between the miconazole and miconazole-loaded chitosan nanoparticles (CS-MCZ) groups insignificant difference (P > 0.05) was observed. Both treatment modalities exhibited comparable effectiveness in controlling oral candidiasis symptoms and reducing Candida colonization as miconazole-loaded chitosan nanoparticles group showed a significant difference in the clinical improvement in respect of both signs and symptoms from baseline (70%) until the end of study at 28 days (5%) (P < 0.05) Moreover, miconazole-loaded chitosan nanoparticles, there was a significant reduction in the number of colonies forming units of Candida albicans from baseline until the end of the study at 28-day with P value < 0.000.
CONCLUSIONS
This randomized controlled clinical trial and microbiological analysis demonstrate that both miconazole and miconazole-loaded chitosan nanoparticles are effective in the treatment of oral candidiasis in diabetic patients with no adverse reactions.
TRIAL REGISTRATION
NCT06072716 with first registration first registration in 10/10/2023.
Topics: Humans; Miconazole; Antifungal Agents; Candidiasis, Oral; Chitosan; Candida; Nanoparticles; Gels; Diabetes Mellitus
PubMed: 38321454
DOI: 10.1186/s12903-024-03952-0 -
Antimicrobial Agents and Chemotherapy Jan 1994A direct study evaluating whether differential drug uptake of topical 2% miconazole and 2% ketoconazole from cream formulations into human stratum corneum correlated... (Comparative Study)
Comparative Study
A direct study evaluating whether differential drug uptake of topical 2% miconazole and 2% ketoconazole from cream formulations into human stratum corneum correlated with differential pharmacological activity against Candida albicans was investigated in healthy human subjects. A single 24-h topical dose of 2% ketoconazole cream or 2% miconazole cream was applied unoccluded, at the same dose (2.6 mg of formulation per cm2 of surface area), at four skin sites on both ventral forearms of six human subjects. At the end of the treatment, residual drug was removed with a tissue from all sites and the treated site was tape stripped 11 times, either 1, 4, 8, or 24 h later. The first tape disc was discarded. The remaining tape discs, 2 through 11, were combined and extracted for drug quantification by high-performance liquid chromatography and bioactivity against C. albicans growth in vitro. Topical 2% ketoconazole produced 14-, 10-, and 7-fold greater drug concentrations in stratum corneum than 2% miconazole at 1, 4, and 8 h after a single topical dose. Ketoconazole and miconazole concentrations in the stratum corneum were similar 24 h after drug removal. Tape disc extracts from 2% ketoconazole-treated skin sites demonstrated significantly greater bioactivity in the bioassay than 2% miconazole. The increased efficacy of 2% ketoconazole compared with that of 2% miconazole in vitro reflects their differential uptake into the stratum corneum and inherent pharmacological activity. Tape stripping the drug-treated site in conjunction with a bioassay is therefore a useful approach in the determination of bioavailability of topical antifungal agents.
Topics: Administration, Topical; Adult; Biological Availability; Candida albicans; Chromatography, High Pressure Liquid; Female; Humans; Ketoconazole; Male; Miconazole; Skin; Skin Absorption
PubMed: 8141586
DOI: 10.1128/AAC.38.1.90 -
Basic & Clinical Pharmacology &... Apr 2017Treatment for oral candidiasis in warfarin users may be complicated by drug-drug interactions (DDIs) between warfarin and topically applied antimycotics. However,...
Treatment for oral candidiasis in warfarin users may be complicated by drug-drug interactions (DDIs) between warfarin and topically applied antimycotics. However, current knowledge of these putative DDIs is merely based on case series. We therefore performed a cohort cross-over study with the objective to evaluate the potential DDIs between warfarin and miconazole oral gel or nystatin oral solution. The cohort consisted of individuals using warfarin in the period of 1998-2012 (n ≈ 7400). We collected data on cohort members' measurements of the international normalized ratio (INR) from a clinical database, and obtained information on their use of topically applied miconazole and nystatin from a regional prescription register. Potential DDIs were assessed by comparing INR values before and after initiation of an antimycotic drug. Among 17 warfarin users exposed to miconazole oral gel, the mean INR increased from 2.5 (95% CI: 2.1-2.8) to 3.8 (95% CI: 2.8-4.8) after exposure, corresponding to a mean INR increase of 1.4 (95% CI: 0.3-2.4). Among 30 warfarin users exposed to nystatin oral solution, the mean INR was 2.7 (95% CI: 2.3-3.1) before and 2.5 (95% CI: 2.2-2.9) after exposure. In conclusion, we found evidence supporting a clinically relevant drug-drug interaction between warfarin and miconazole oral gel. In contrast, we did not find any indication of an interaction between warfarin and nystatin oral solution. Nystatin rather than miconazole should be preferred when treating warfarin users for oral candidiasis.
Topics: Administration, Oral; Aged; Antifungal Agents; Blood Coagulation; Candidiasis, Oral; Cohort Studies; Cross-Over Studies; Drug Interactions; Female; Gels; Humans; International Normalized Ratio; Male; Miconazole; Middle Aged; Nystatin; Solutions; Warfarin
PubMed: 27901310
DOI: 10.1111/bcpt.12722 -
Cancer Science Jul 2020DNA damage-induced apoptosis suppressor (DDIAS) facilitates the survival of lung cancer by suppressing apoptosis. Moreover, DDIAS promotes tyrosine phosphorylation of...
DNA damage-induced apoptosis suppressor (DDIAS) facilitates the survival of lung cancer by suppressing apoptosis. Moreover, DDIAS promotes tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3) via their interaction. Here, we identified miconazole as an inhibitor of DDIAS/STAT3 interaction by screening a chemical library using a yeast two-hybrid assay. Miconazole inhibited growth, migration and invasion of lung cancer cells. Furthermore, miconazole suppressed STAT3 tyrosine Y705 phosphorylation and the expression of its target genes, such as cyclin D1, survivin and snail but had no suppressive effect on the activation of ERK1/2 or AKT, which is involved in the survival of lung cancer. As expected, no interaction between DDIAS and STAT3 occurred in the presence of miconazole, as confirmed by immunoprecipitation assays. Mouse xenograft experiments showed that miconazole significantly suppressed both tumor size and weight in an NCI-H1703 mouse model. Tyrosine phosphorylation of STAT3 at Y705 and expression of its targets, such as cyclin D1, survivin and snail, were decreased in miconazole-treated tumor tissues, as compared with those in vehicle-treated tumor tissues. These data suggest that miconazole exerts an anti-cancer effect by suppressing STAT3 activation through inhibiting DDIAS/STAT3 binding.
Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; DNA Damage; Disease Models, Animal; Drug Screening Assays, Antitumor; Gene Expression; Genes, Reporter; Humans; Mice; Miconazole; Phosphorylation; STAT3 Transcription Factor; Signal Transduction; Xenograft Model Antitumor Assays
PubMed: 32476221
DOI: 10.1111/cas.14432 -
Genes Sep 20235-methylcytosine (5mC) is one of the most important epigenetic modifications. Its increased occurrence in regulatory sequences of genes, such as promoters and enhancers,...
5-methylcytosine (5mC) is one of the most important epigenetic modifications. Its increased occurrence in regulatory sequences of genes, such as promoters and enhancers, is associated with the inhibition of their expression. Methylation patterns are not stable but are sensitive to factors such as the environment, diet, and age. In the present study, we investigated the effects of fungicide miconazole, both alone and in combination with the insecticide Mospilan 20SP, on the methylation status of bovine , , and genes in bovine lymphocytes cultured in vitro. The methylation-specific PCR technique was used for the objectives of this study. We found that miconazole alone at concentrations of 1.25, 2.5, 5, 10, 25, and 50 µg/mL after 24 h exposure probably did not induce changes in methylation for all three genes analysed. The same results were found for the combination of pesticides at 24 h exposure and the following concentrations for each of them: 0.625, 1.25, 2.5, 5, and 12.5 µg/mL. Thus, we can conclude that the fungicide miconazole alone, as well as in combination with the insecticide Mospilan 20SP, was unlikely to cause changes to the methylation of bovine , , and genes.
Topics: Animals; Cattle; Fungicides, Industrial; Insecticides; Lymphocytes; Methylation; Miconazole; Glutathione S-Transferase pi; Glutathione Transferase; Acetylcholinesterase
PubMed: 37761931
DOI: 10.3390/genes14091791 -
Frontiers in Cell and Developmental... 2020Fungal biofilm-related infections are increasingly occurring. We previously identified a fungicidal antibiofilm combination, consisting of miconazole (MCZ) and the...
Fungal biofilm-related infections are increasingly occurring. We previously identified a fungicidal antibiofilm combination, consisting of miconazole (MCZ) and the quaternary ammonium compound domiphen bromide (DB). DB eliminates tolerance rather than altering the susceptibility to MCZ of various spp. Here we studied the mode of action of the MCZ-DB combination in more detail. We found that DB's action increases the permeability of the plasma membrane as well as that of the vacuolar membrane of spp. Furthermore, the addition of DB affects the intracellular azole distribution. MCZ is a fungicidal azole that, apart from its well-known inhibition of ergosterol biosynthesis, also induces accumulation of reactive oxygen species (ROS). Interestingly, the MCZ-DB combination induced significantly more ROS in biofilms as compared to single compound treatment. Co-administration of the antioxidant ascorbic acid resulted in abolishment of the ROS generated by MCZ-DB combination as well as its fungicidal action. In conclusion, increased intracellular MCZ availability due to DB's action results in excess of ROS and enhanced fungal cell killing.
PubMed: 33553152
DOI: 10.3389/fcell.2020.617214 -
Resurgence and Repurposing of Antifungal Azoles by Transition Metal Coordination for Drug Discovery.Pharmaceutics Sep 2023Coordination compounds featuring one or more antifungal azole (AA) ligands constitute an interesting family of candidate molecules, given their medicinal polyvalence and... (Review)
Review
Coordination compounds featuring one or more antifungal azole (AA) ligands constitute an interesting family of candidate molecules, given their medicinal polyvalence and the viability of drug complexation as a strategy to improve and repurpose available medications. This review reports the work performed in the field of coordination derivatives of AAs synthesized for medical purposes by discussing the corresponding publications and emphasizing the most promising compounds discovered so far. The resulting overview highlights the efficiency of AAs and their metallic species, as well as the potential still lying in this research area.
PubMed: 37896159
DOI: 10.3390/pharmaceutics15102398 -
Veterinary Research Communications Aug 2009The therapeutic value of antibiotics depends on the susceptibility of the infecting microorganism and the pharmacological profile of the drugs. To assess the value of an...
The therapeutic value of antibiotics depends on the susceptibility of the infecting microorganism and the pharmacological profile of the drugs. To assess the value of an antibiotic combination of polymyxin B and miconazole this study examined the in vitro synergistic potential of the two drugs on Gram-negative and Gram-positive bacteria and yeast. Antifungal and antibacterial activity was tested by minimum inhibitory concentration (MIC) of broth macrodilution and urea broth microdilution, by fluorescence microscopy and flow cytometry. Synergism was calculated using the fractional inhibitory concentration index (FICi). With Staphylococcus intermedius as target we found up to an eightfold reduction of the individual MICs when both drugs were combined. However, the FICi was 0.63 suggesting no real interaction between the two drugs. With Escherichia coli, Pseudomonas aeruginosa, and Malassezia pachydermatis as targets the antimicrobial drug combination reduced the MICs of polymyxin B and miconazole from fourfold to hundredfold resulting in FICi between 0.06 and 0.5 which defines a synergistic action. Thus, if polymyxin B and miconazole are combined their effect is greater than the sum of the effects observed with polymyxin B and miconazole independently, revealing bactericidal and fungicidal synergism. Our results indicate a strong therapeutic value for the combination of these antimicrobial agents against Gram-negative bacteria and yeast and a weaker value against Gram positive bacteria for clinical situations where these pathogens are involved.
Topics: Anti-Bacterial Agents; Antifungal Agents; Bacteria; Culture Media; Drug Combinations; Drug Synergism; Escherichia coli; Flow Cytometry; Malassezia; Miconazole; Microbial Sensitivity Tests; Microscopy, Fluorescence; Polymyxin B; Pseudomonas aeruginosa; Staphylococcus intermedius; Urea
PubMed: 19085068
DOI: 10.1007/s11259-008-9194-z -
American Journal of Rhinology & Allergy 2012Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Because fungi were postulated as a potential cause of CRS in the late 1990s,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Because fungi were postulated as a potential cause of CRS in the late 1990s, contrasting articles have advocated and refuted the use of antifungal agents in its management. Although good research shows an interaction of the immune system with fungus in CRS, e.g., allergic fungal sinusitis (AFS), this does not imply that fungi are the cause of CRS or that antifungals will be effective in management. This study was designed to assess the potential advantage of either topical or systemic antifungal therapy in the symptomatic treatment of CRS to aid physicians in making informed decisions about treating patients with CRS.
METHODS
A systematic review of the literature was performed with meta-analysis. All studies obtained from searches were reviewed and trials meeting the eligibility criteria were selected. CRS was defined using either the European Position Paper on Rhinosinusitis and Nasal Polyps or American Academy of Otolaryngology-Head and Neck Surgery criteria. Authors were contacted and original data were used for data analysis.
RESULTS
Five studies investigating topical antifungals and one investigating systemic antifungals met the inclusion criteria. All trials were double blinded and randomized. Pooled meta-analysis showed no statistically significant benefit of topical or systemic antifungals over placebo. Symptoms scores statistically favored the placebo group for this outcome. Adverse event reporting was higher in the antifungal group.
CONCLUSION
Reported side-effects of antifungal therapies may outweigh any potential benefits of treatment based on this meta-analysis and the authors therefore do not advocate the use antifungal treatment in the management of CRS.
Topics: Antifungal Agents; Chronic Disease; Disease Management; Humans; Miconazole; Mycoses; Randomized Controlled Trials as Topic; Rhinitis; Sinusitis; Treatment Outcome
PubMed: 22487292
DOI: 10.2500/ajra.2012.26.3710 -
International Journal of Molecular... Feb 2021In a previous article, we reported on the higher toxicity of silver(I) complexes of miconazole [Ag(MCZ)NO ()] and [Ag(MCZ)ClO ()] in HepG2 tumor cells compared to the...
In a previous article, we reported on the higher toxicity of silver(I) complexes of miconazole [Ag(MCZ)NO ()] and [Ag(MCZ)ClO ()] in HepG2 tumor cells compared to the corresponding salts of silver, miconazole and cisplatin. Here, we present the synthesis of two silver(I) complexes of miconazole containing two new counter ions in the form of Ag(MCZ)X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole]; X = BF (), SbF ()). The novel silver(I) complexes were characterized by elemental analysis, H NMR, C NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry and X-ray-crystallography. In the present study, the antimicrobial activity of all obtained silver(I) complexes of miconazole against six strains of Gram-positive bacteria, five strains of Gram-negative bacteria and yeasts was evaluated. The results were compared with those of a silver sulfadiazine drug, the corresponding silver salts and the free ligand. Silver(I) complexes exhibited significant activity against Gram-positive bacteria, which was much better than that of silver sulfadiazine and silver salts. The highest antimicrobial activity was observed for the complex containing the nitrate counter ion. All Ag(I) complexes of miconazole resulted in much better inhibition of yeast growth than silver sulfadiazine, silver salts and miconazole. Moreover, the synthesized silver(I) complexes showed good or moderate activity against Gram-negative bacteria compared to the free ligand.
Topics: Anti-Bacterial Agents; Antifungal Agents; Coordination Complexes; Gram-Negative Bacteria; Gram-Positive Bacteria; Miconazole; Silver; Yeasts
PubMed: 33546211
DOI: 10.3390/ijms22041510