-
Brain and Behavior Oct 2019Peripheral nerve injury (PNI) causes motor and sensory defects, has strong impact on life quality and still has no effective therapy. Miconazole is one of the most...
BACKGROUND
Peripheral nerve injury (PNI) causes motor and sensory defects, has strong impact on life quality and still has no effective therapy. Miconazole is one of the most widely used antifungal drugs; the aims of the study were to investigate the effects of miconazole during sciatic nerve regeneration in a mouse model of sciatic nerve crush injury.
METHODS
We established peripheral nerve crush model and investigated the effects of miconazole by multiple aspects. We further studied the potential mechanism of action of miconazole by Western blotting, fluorescence immunohistochemistry, and PCR analysis.
RESULTS
Miconazole improves the symptoms of crushed nerve by improving inflammatory cell infiltration and demyelinating myelin of sciatic nerve. Affected by miconazole, the proportion of inflammatory M1 macrophages in the distal part of the sciatic nerve was reduced, and the proportion of anti-inflammatory M2 macrophages was increased. Finally, the neuroprotective properties of miconazole may be regulated by the nuclear factor (NF)-κB pathway.
CONCLUSIONS
Our data suggest that miconazole can effectively alleviate PNI, and the mechanism involves mediating a phenotype change of M1/ M2 macrophages. Thus, miconazole may represent a potential therapeutic intervention for nerve crush injury.
Topics: Animals; Crush Injuries; Cytochrome P-450 CYP2C9 Inhibitors; Disease Models, Animal; Macrophages; Male; Mice; Mice, Inbred C57BL; Miconazole; NF-kappa B; Nerve Crush; Nerve Regeneration; Peripheral Nerve Injuries; Phenotype; Sciatic Nerve
PubMed: 31486271
DOI: 10.1002/brb3.1400 -
International Journal of Nanomedicine 2018The current study was aimed at developing a novel mucoadhesive thiolated cyclodextrin (CD) without ionizable groups and an intact ring backbone for drug delivery.
INTRODUCTION
The current study was aimed at developing a novel mucoadhesive thiolated cyclodextrin (CD) without ionizable groups and an intact ring backbone for drug delivery.
MATERIALS AND METHODS
Thiolated beta CD (β-CD) was prepared through bromine substitution of its hydroxyl groups followed by replacement to thiol groups using thiourea. The thiolated β-CD was characterized in vitro via dissolution studies, cytotoxicity studies, mucoadhesion studies on freshly excised porcine intestinal mucosa, and inclusion complex formation with miconazole nitrate.
RESULTS
Thiolated β-CDs namely β-CD-SH and β-CD-SH displayed 558.66 ± 78 and 1,163.45 ± 96 µmol thiol groups per gram of polymer, respectively. Stability constant (Kc) of 190 M confirmed the inclusion complex formation of miconazole nitrate with β-CD-SH. Inclusion complexes of β-CD-SH and β-CD-SH resulted in 157- and 257-fold increased solubility of miconazole nitrate, respectively. In addition, more than 80% of thiol groups were stable even after 6 hours at pH 5. Both β-CD-SH compounds showed at least 1.3-fold improved solubility in water. In contrast to cationic thiolated CDs of the first generation, both thiomers showed no significant cytotoxicity. The mucoadhesive properties of the new thiolated CDs were 39.73- and 46.37-fold improved, respectively.
CONCLUSION
These results indicate that β-CD-SH might provide a new favorable tool for delivery of poorly soluble drugs providing a prolonged residence time on mucosal surfaces.
Topics: Adhesiveness; Animals; Caco-2 Cells; Cell Death; Chromatography, Liquid; Drug Delivery Systems; Humans; Humidity; Hydrogen-Ion Concentration; Intestinal Mucosa; Ions; Mass Spectrometry; Miconazole; Solubility; Sulfhydryl Compounds; Swine; Time Factors; Water; beta-Cyclodextrins
PubMed: 30022823
DOI: 10.2147/IJN.S153226 -
Journal of Traditional Chinese Medicine... Aug 2022To summarize and evaluate the effectiveness and safety of Redcore lotion on treating vulvovaginal candidiasis (VVC) using a systematic review and Meta-analysis of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To summarize and evaluate the effectiveness and safety of Redcore lotion on treating vulvovaginal candidiasis (VVC) using a systematic review and Meta-analysis of randomized controlled trials.
METHODS
A systematic literature search was performed in five English and three Chinese electronic databases up to October 2019. Randomized controlled trials in the treatment for VVC were included; only studies which compared the effectiveness and safety of Redcore lotion plus miconazole with miconazole alone were included. Relative risk (RR) and 95% confidence intervals (CI) were used in the Meta-analysis.
RESULTS
Seven studies involving 768 patients suffering from VVC were identified; 468 of the patients were pregnant women (60.9%). Combination group (Redcore lotion plus miconazole) was more effective in reduCIng symptomatic episodes of VVC than miconazole alone, with respect to cure rate (RR, 1.31; 95% CI, 1.09-1.57; P = 0.01), fungal culture negative rate (RR, 1.21; 95% CI, 1.04-1.41; P = 0.01), and effective rate (RR, 1.18; 95% CI, 1.05-1.35; P = 0.01). Subgroup analyses for pregnant women also showed that the combination group had superior outcomes with respect to VVC cure rate (RR, 1.48; 95% CI, 1.16-1.88, P < 0.01), fungal culture negative rate (RR, 1.26; 95% CI; 1.09-1.47; P < 0.01), and effective rate (RR, 1.25; 95% CI, 1.10-1.42; P < 0.01). Additionally, the observed risk of adverse events was lower in the combination medication group (RR, 0.30; 95% CI, 0.14-0.65; P < 0.01).
CONCLUSIONS
Though overall quality of individual studies was low, Redcore lotion plus miconazole can significantly improve clinical effectiveness and safety compared with miconazole alone.
Topics: Candidiasis, Vulvovaginal; Female; Humans; Miconazole; Pregnancy; Treatment Outcome
PubMed: 35848964
DOI: 10.19852/j.cnki.jtcm.2022.04.001 -
AAPS PharmSciTech 2008The aim of this study is to confirm the formation of inclusion complexes between miconazole (MCZ) and two derivatives of beta-cyclodextrin, methyl-beta-cyclodextrin...
The aim of this study is to confirm the formation of inclusion complexes between miconazole (MCZ) and two derivatives of beta-cyclodextrin, methyl-beta-cyclodextrin (MbetaCD) and 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) in aqueous solution by phase solubility studies. Inclusion complexes with MbetaCD in the solid state were then prepared by different methods, i.e., kneading, coevaporation (COE), spray-drying (SD), and lyophilization (LPh). The physicochemical properties of these complexes were subsequently studied by means of differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction techniques. Phase solubility diagrams with MbetaCD and HPbetaCD were classified as A(P) type, indicating the formation of 1:1 and 1:2 stoichiometric inclusion complexes. The apparent stability constants (K(S)) calculated from the phase solubility diagram were 145.69 M(-1) (K(1:1)) and 11.11 M(-1) (K(1:2)) for MbetaCD and 126.94 M(-1) (K(1:1)) and 2.20 M(-1) (K(1:2)) for HPbetaCD. The method of preparation of the inclusion complexes in the solid state was shown to greatly affect the properties of the formed complex. Hence, the LPh, SD, and COE methods produce true inclusion complexes between MCZ and MbetaCD. In contrast, crystalline drug was still clearly detectable in the kneaded (KN) product.
Topics: Antifungal Agents; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Miconazole; Microscopy, Electron, Scanning; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction; beta-Cyclodextrins
PubMed: 18975116
DOI: 10.1208/s12249-008-9143-8 -
Indian Journal of Dermatology,... 2020
Topics: Anticoagulants; Antifungal Agents; Drug Interactions; Humans; Miconazole; Warfarin
PubMed: 33037157
DOI: 10.4103/ijdvl.IJDVL_515_18 -
Journal of Physiology and Pharmacology... Oct 2016The formation of biofilms by Candida and the increasing resistance of Candida species to antifungals contribute to the high recurrence rates of denture stomatitis. This...
The formation of biofilms by Candida and the increasing resistance of Candida species to antifungals contribute to the high recurrence rates of denture stomatitis. This increase has stimulated an interest in antimicrobial photodynamic therapy (aPDT) as an alternative treatment. We examined the photoactivity of the porphyrin-based photosensitizer, TMP-1363, against biofilms of C. albicans, C. glabrata, C. tropicalis and C. parapsilosis, and the effect of the combined use of miconazole and aPDT. Biofilms of three American Type Culture Collection (ATCC) strains and four clinical isolates developed on poly(methyl methacrylate) (PMMA) disks, were incubated with miconazole, followed by treatment with TMP-1363 for 30 min at 37°C. The plates were exposed to broadband visible light at a distance of 10 cm to the plate, for 30 min (irradiance at the surface of the plate: 32.5 mW/cm2). The metabolic activity of the biofilms was measured by the XTT assay. ATCC strains and C. glabrata 7531/06 were not sensitive to TMP-aPDT, whereas the metabolic activities of the remaining three clinical isolates were reduced to 64.2 ± 5.5% of controls. Miconazole at 25 μg/ml decreased the viability of all strains except the ATTCC strain C. albicans MYA274; however its combination with aPDT was effective against this strain, suggesting a synergistic interaction. Effects of miconazole and aPDT on C. albicans MYA 2732, C. albicans 6122/06 were additive. With C. tropicalis and C. parapsilosis, the combined treatment had a higher, but not entirely additive, cytotoxic effect. The combined use of miconazole and TMP-aPDT is advantageous in the treatment of biofilms of a number of Candida species and strains, but not all. The molecular basis of this differential response is not known.
Topics: Antifungal Agents; Biofilms; Candida; Light; Miconazole; Photochemotherapy; Photosensitizing Agents; Porphyrins
PubMed: 28011958
DOI: No ID Found -
Advanced Biomedical Research 2013One of the most common causes of vaginitis is candidiasis. The aim of this study is to compare the effect of honey and miconazole against Candida albicans, in vitro.
BACKGROUND
One of the most common causes of vaginitis is candidiasis. The aim of this study is to compare the effect of honey and miconazole against Candida albicans, in vitro.
MATERIALS AND METHODS
The different W/V concentrations of honey were prepared at 20, 40, 60, 80, and 95% and different dilutions of miconazole were prepared in 0.05, 5, and 50 μg/ml. A microdilution of 100/000 cells per ml of a two-day old culture of Candida albicans was prepared in normal saline, after culturing the strain of PTCC 5027 in RPMI 1640 medium. Ten microliters of this dilution was added to 1 ml of the RPMI 1640 medium containing different concentrations of honey and to 1 ml of the RPMI 1640 medium containing different dilutions of miconazole. The cultures were incubated at 35°C for 12, 24, and 48 hours.
RESULTS
The growth rate of Candida albicans was determined in the cultures. The results indicated that the honey prevented the growth of C. albicans greatly only at an 80% concentration, whereas, miconazole inhibited it completely.
CONCLUSIONS
As Candida albicans is a normal vaginal flora, the inhibitory effect of honey without the fungicide effect is a very good trend in the treatment of vaginal candidiasis.
PubMed: 24223372
DOI: 10.4103/2277-9175.115800 -
In Vivo Evaluation of Miconazole-Nitrate-Loaded Transethosomal Gel Using a Rat Model Infected with .Pharmaceuticals (Basel, Switzerland) Apr 2024Miconazole nitrate (MCNR), an antifungal drug, is used to treat superficial infections. The objective of the current study was to assess the antifungal effectiveness of...
Miconazole nitrate (MCNR), an antifungal drug, is used to treat superficial infections. The objective of the current study was to assess the antifungal effectiveness of MCNR-loaded transethosomal gel (MNTG) against in an in vivo rat model. The outcomes were compared with those of the miconazole nitrate gel (MNG) and marketed Daktarin cream (2%) based on histopathological and hematological studies. The results of the skin irritation test revealed the safety profile of the MNTG. The MNTG demonstrated the greatest antifungal activity in the histological analysis and the visible restoration of the skin, and the rats revealed an apparent evidence of recovery. Compared to the untreated group, the treated group's lymphocyte and white blood cells counts increased, but their eosinophil counts decreased. In conclusion, MNTG exhibited the greatest antifungal activity, which might be connected to the improved skin permeability of the transethosome's nanosized vesicles. Therefore, it could be considered a promising carrier for topical usage and the treatment of cutaneous candidiasis. More clinical research needs to be performed in order to demonstrate its effectiveness and safe usage in humans.
PubMed: 38794118
DOI: 10.3390/ph17050546 -
Scientific Reports Jun 2019Fungi respond to antifungal drugs by increasing their antioxidant stress response. How this impacts antifungal efficacy remains controversial and not well understood....
Fungi respond to antifungal drugs by increasing their antioxidant stress response. How this impacts antifungal efficacy remains controversial and not well understood. Here we examine the role of catalase activity in the resistance of Saccharomyces cerevisiae to the common antifungals, fluconazole and miconazole, for which we report minimum inhibitory concentrations (MICs) of 104 and 19 μM, respectively. At sub-MIC concentrations, fluconazole and miconazole stimulate catalase activity 2-3-fold but, unexpectedly, deletion of cytosolic catalase (ctt1) makes cells more resistant to these azoles and to clotrimazole, itraconazole and posaconazole. On the other hand, upregulating Ctt1 activity by preconditioning with 0.2 mM HO potentiates miconazole 32-fold and fluconazole 4-fold. Since HO preconditioning does not alter the resistance of ctt1Δ cells, which possess negligible catalase activity, we link azole potentiation with Ctt1 upregulation. In contrast, sod2Δ cells deleted for mitochondrial superoxide dismutase are 4-8-fold more azole sensitive than wild-type cells, revealing that Sod2 activity protects cells against azole toxicity. In fact, the ctt1Δ mutant has double the Sod2 activity of wild-type cells so ctt1 deletion increases azole resistance in part by Sod2 upregulation. Notably, deletion of peroxisomal/mitochondrial cta1 or cytosolic sod1 does not alter fluconazole or miconazole potency.
Topics: Antifungal Agents; Azoles; Catalase; Drug Resistance, Fungal; Gene Expression Regulation, Fungal; Gene Knockout Techniques; Hydrogen Peroxide; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Superoxide Dismutase
PubMed: 31235707
DOI: 10.1038/s41598-019-45070-w -
Molecules (Basel, Switzerland) May 2024The main objective of this study was to investigate the metabolism of miconazole, an azole antifungal drug. Miconazole was subjected to incubation with human liver...
Identification of New Hepatic Metabolites of Miconazole by Biological and Electrochemical Methods Using Ultra-High-Performance Liquid Chromatography Combined with High-Resolution Mass Spectrometry.
The main objective of this study was to investigate the metabolism of miconazole, an azole antifungal drug. Miconazole was subjected to incubation with human liver microsomes (HLM) to mimic phase I metabolism reactions for the first time. Employing a combination of an HLM assay and UHPLC-HRMS analysis enabled the identification of seven metabolites of miconazole, undescribed so far. Throughout the incubation with HLM, miconazole underwent biotransformation reactions including hydroxylation of the benzene ring and oxidation of the imidazole moiety, along with its subsequent degradation. Additionally, based on the obtained results, screen-printed electrodes (SPEs) were optimized to simulate the same biotransformation reactions, by the use of a simple, fast, and cheap electrochemical method. The potential toxicity of the identified metabolites was assessed using various in silico models.
Topics: Miconazole; Humans; Chromatography, High Pressure Liquid; Microsomes, Liver; Mass Spectrometry; Electrochemical Techniques; Antifungal Agents; Biotransformation
PubMed: 38731651
DOI: 10.3390/molecules29092160