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Pharmaceutics Feb 2024This research aimed to develop miconazole-based microemulsions using oleic acid as a natural lipophilic phase and a stabilizer mixture comprising Tween 20 and PEG 400 to...
This research aimed to develop miconazole-based microemulsions using oleic acid as a natural lipophilic phase and a stabilizer mixture comprising Tween 20 and PEG 400 to solubilize miconazole as an antifungal agent known for its activity in oral candidiasis and to improve its bioavailability. The formulation and preparation process was combined with a mathematical approach using a 2-full factorial plan. Fluid and gel-like microemulsions were obtained and analyzed considering pH, conductivity, and refractive index, followed by extensive analyses focused on droplet size, zeta potential, rheological behavior, and goniometry. In vitro release tests were performed to assess their biopharmaceutical characteristics. Independent variables coded X-Oleic acid (%, /), X-Tween 20 (%, /), and X-PEG 400 (%, /) were analyzed in relationship with three main outputs like mean droplet size, work of adhesion, and diffusion coefficient by combining statistical tools with response surface methodology. The microemulsion containing miconazole base-2%, oleic acid-5%, Tween 20-40%, PEG 400-20%, and water-33% exhibited a mean droplet size of 119.6 nm, a work of adhesion of 71.98 mN/m, a diffusion coefficient of 2.11·10 cm/s, and together with remarked attributes of two gel-like systems formulated with higher oil concentrations, modeled the final optimization step of microemulsions as potential systems for buccal delivery.
PubMed: 38399325
DOI: 10.3390/pharmaceutics16020271 -
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 -
Frontiers in Neurology 2023One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms...
One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms underlying potassium channels in human TLE have not yet been elucidated. Hence, this study aimed to mine potassium channel genes linked to TLE using a bioinformatic approach. The results found that Four key TLE-related potassium channel genes (TERKPCGs) were identified: potassium voltage-gated channel subfamily E member () 1, , potassium inwardly rectifying channel, subfamily J, member 11 (), and . A protein-protein interaction (PPI) network was constructed to analyze the relationship between TERKPCGs and other key module genes. The results of gene set enrichment analysis (GSEA) for a single gene indicated that the four TERKPCGs were highly linked to the cation channel, potassium channel, respiratory chain, and oxidative phosphorylation. The mRNA-TF network was established using four mRNAs and 113 predicted transcription factors. A ceRNA network containing seven miRNAs, two mRNAs, and 244 lncRNAs was constructed based on the TERKPCGs. Three common small-molecule drugs (enflurane, promethazine, and miconazole) target , and . Ten small-molecule drugs (glimepiride, diazoxide, levosimendan, and thiamylal et al.) were retrieved for . Compared to normal mice, the expression of , , , and was downregulated in the brain tissue of the epilepsy mouse model at both the transcriptional and translational levels, which was consistent with the trend of human data from the public database. The results indicated that key potassium channel genes linked to TLE were identified based on bioinformatics analysis to investigate the potential significance of potassium channel genes in the development and treatment of TLE.
PubMed: 37483435
DOI: 10.3389/fneur.2023.1175007 -
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 -
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 -
Women's Health Reports (New Rochelle,... 2022Recurrent vulvovaginal candidiasis (RVVC), defined as three or more confirmed infections over 1 year, occurs in up to 10% of women. In these women, the objective is...
Recurrent vulvovaginal candidiasis (RVVC), defined as three or more confirmed infections over 1 year, occurs in up to 10% of women. In these women, the objective is often symptomatic control rather than mycologic cure. Current Centers for Disease Control and Prevention (CDC) guidelines recommend oral fluconazole as first-line maintenance, but state if this oral regimen is not feasible, intermittent topical treatments can be considered. No specific recommendations for type or frequency of topical applications are provided by the CDC. A panel of vulvovaginal experts convened to develop a consensus recommendation for topical maintenance dosing for RVVC. Data suggest that clotrimazole, miconazole, terconazole, and intravaginal boric acid are suggested recommendations for recurrent vulvovaginitis caused by both and nonalbicans species. Nystatin ovules may not be as effective as azoles. Identification of species will influence treatment decisions. In addition, treatment may be modified based on prior response to a specific agent, especially in nonalbicans species. Fluconazole, ibrexafungerp, and intravaginal boric acid should be avoided during pregnancy. The expert consensus for women with RVVC is an initial full course of treatment followed by topical maintenance beginning at one to three times weekly, based on chosen agent. Twice a week dosing was the regimen most often utilized. In some women, episodic treatment may be used, but maintenance should remain an option for this population.
PubMed: 35136875
DOI: 10.1089/whr.2021.0065 -
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 -
Frontiers in Pediatrics 2022The use of antimicrobial-impregnated peripherally inserted central catheters (PICCs) has been introduced in the last few years to neonatal units aiming to reduce central...
BACKGROUND
The use of antimicrobial-impregnated peripherally inserted central catheters (PICCs) has been introduced in the last few years to neonatal units aiming to reduce central line-associated bloodstream infection (CLABSI).
METHODS
This retrospective observational study aimed to compare the CLABSI rates and other catheter-related parameters including the insertion success rates and catheter-related complications in the antimicrobial-impregnated and conventional (ordinary) PICCs in NICU between 2017 and 2020.
RESULTS
Our dedicated PICC team including physicians and nurses inserted 1,242 conventional (PremiCath and NutriLine) and 791 antimicrobial-impregnated PICCs (PremiStar) over the study period from 2017 to 2020. Of those 1,242 conventional PICCs, 1,171 (94.3%) were 1 Fr single lumen and only 71 (5.7%) were 2 Fr double lumen. The mean ± SD [median (IQR)] for the birth weight in all babies who had a PICC line was 1,343.3 ± 686.75 [1,200 (900, 1,500)] g, while the mean ± SD for the gestational age was 29.6 ± 4.03 [29 (27, 31)] weeks. The mean ± SD [median (IQR)] age at the time of insertion for all catheters was 9.3 ± 21.47 [2 (1, 9)] days, while the mean ± SD [median (IQR)] dwell time was 15.7 ± 14.03 [12 (8, 17)] days. The overall success rate of the PICC insertion is 1,815/2,033 (89.3%), while the first attempt success rate is 1,290/2,033 (63.5%). The mean ± SD [median (IQR)] gestational age, birth weight, age at catheter insertion, and catheter dwell time were 28.8 ± 3.24 [29, (26, 31)] weeks, 1,192.1 ± 410.3 [1,150, (900, 1,450)] g, 6.3 ± 10.85 [2, (1, 8)] days, and 17.73 ± 17.532 [13, (9, 18)] days in the antimicrobial-impregnated catheter compared with 30.1 ± 4.39 [29, (27, 32)] weeks ( < 0.001), 1,439.5 ± 800.8 [1,240, (920, 1,520)] g ( < 0.001), 11.1 ± 25.9 [1, (1, 9)] days ( < 0.001), and 14.30 ± 10.964 [12, (8, 17)] days ( < 0.001), respectively, in the conventional PICCs. The use of the antimicrobial-impregnated catheter was not associated with any significant reduction in the CLABSI rate (per 1,000 days dwell time), either the overall [ = 0.11, risk ratio (RR) (95% CI): 0.60 (0.32, 1.13)] or the yearly CLABSI rates.
CONCLUSIONS
The use of miconazole and rifampicin-impregnated PICCs did not reduce the CLABSI rate in neonates compared with conventional PICCs. However, it has a higher overall rate of elective removal after completion of therapy and less extravasation/infiltration, occlusion, and phlebitis compared with the conventional PICCs. Further large RCTs are recommended to enrich the current paucity of evidence and to reduce the risk of bias. Neonatal PICCs impregnation by other antimicrobials is a recommendation for vascular access device manufacturers.
PubMed: 36507144
DOI: 10.3389/fped.2022.1012800 -
Indian Journal of Dermatology,... 2020
Topics: Anticoagulants; Antifungal Agents; Drug Interactions; Humans; Miconazole; Warfarin
PubMed: 33037157
DOI: 10.4103/ijdvl.IJDVL_515_18 -
Pharmaceutics Oct 2023Miconazole nitrate (MCNR) is a BCS class II antifungal drug with poor water solubility. Although numerous attempts have been made to increase its solubility, formulation...
Miconazole nitrate (MCNR) is a BCS class II antifungal drug with poor water solubility. Although numerous attempts have been made to increase its solubility, formulation researchers struggle with this significant issue. Transethosomes are promising novel nanocarriers for improving the solubility and penetration of drugs that are inadequately soluble and permeable. Thus, the objective of this study was to develop MCNR-loaded transethosomal gel in order to enhance skin permeation and antifungal activity. MCNR-loaded transethosomes (MCNR-TEs) were generated using the thin film hydration method and evaluated for their zeta potential, particle size, polydispersity index, and entrapment efficiency (EE%). SEM, FTIR, and DSC analyses were also done to characterize the optimized formulation of MCNR-TEs (MT-8). The optimized formulation of MCNR-TEs was incorporated into a carbopol 934 gel base to form transethosomal gel (MNTG) that was subjected to ex vivo permeation and drug release studies. In vitro antifungal activity was carried out against through the cup plate technique. An in vivo skin irritation test was also performed on Wistar albino rats. MT-8 displayed smooth spherical transethosomal nanoparticles with the highest EE% (89.93 ± 1.32%), lowest particle size (139.3 ± 1.14 nm), polydispersity index (0.188 ± 0.05), and zeta potential (-18.1 ± 0.10 mV). The release profile of MT-8 displayed an initial burst followed by sustained release, and the release data were best fitted with the Korsmeyer-Peppas model. MCNR-loaded transethosomal gel was stable and showed a non-Newtonian flow. It was found that ex vivo drug permeation of MNTG was 48.76%, which was significantly higher than that of MNPG (plain gel) ( ≤ 0.05) following a 24-h permeation study. The prepared MCNR transethosomal gel exhibited increased antifungal activity, and its safety was proven by the results of an in vivo skin irritation test. Therefore, the developed transethosomal gel can be a proficient drug delivery system via a topical route with enhanced antifungal activity and skin permeability.
PubMed: 38004517
DOI: 10.3390/pharmaceutics15112537