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Molecules (Basel, Switzerland) May 2024The theoretical interpretation of the vaginal permeability phenomenon, the evaluation of the suitability of five artificial membranes, and the prediction of the... (Comparative Study)
Comparative Study
The theoretical interpretation of the vaginal permeability phenomenon, the evaluation of the suitability of five artificial membranes, and the prediction of the behaviors of vaginal drugs were the main objectives of this study. Franz vertical diffusion cells and different validated HPLC methods were used to measure the permeability of six vaginally administered drugs (econazole, miconazole, metronidazole, clindamycin, lidocaine, and nonoxynol-9). This study was performed (in vitro) on different membranes of polyvinylidene fluoride (PVDF), plain cellulose or cellulose impregnated with isopropyl myristate (IPM), and cellulose combined with PVDF or IPM. The results were compared with those obtained from cow vaginal tissue (ex vivo), where cellulose was proven to be the best simulant. According to the permeability profiles (P), the water solubility of the drugs was considered a necessary criterion for their transport in the membranes or in the tissue, while the size was important for their penetration. Furthermore, it was found that polar compounds show clear superiority when penetrating cellulose or tissue, while non-polar ones show superiority when penetrating the lipophilic PVDF membrane. Finally, a successful attempt was made to predict the P values (|P-predP| < 0.005) of the six drugs under study based on a PLS (Partial Least Squares) in silico simulation model.
Topics: Female; Membranes, Artificial; Vagina; Permeability; Administration, Intravaginal; Animals; Polyvinyls; Cellulose; Cattle; Humans; Solubility; Fluorocarbon Polymers
PubMed: 38792194
DOI: 10.3390/molecules29102334 -
International Journal of Molecular... May 2024Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new...
Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ)AgNO], [(MTZ)Ag]SO, [Ag(MCZ)NO], [Ag(MCZ)BF], [Ag(MCZ)SbF] and [Ag(MCZ)ClO] (MTZ-metronidazole; MCZ-miconazole) silver(I) compounds and the possible relationship between the molecules and their cytostatic activity against melanoma cells. Molecular Hirshfeld surface analysis and computational methods were used to examine the possible association between the structure and anticancer activity of the silver(I) complexes and compare the cytotoxicity of the silver(I) complexes of metronidazole and miconazole with that of silver(I) nitrate, cisplatin, metronidazole and miconazole complexes against A375 and BJ cells. Additionally, these preliminary biological studies found the greatest IC values against the A375 line were demonstrated by [Ag(MCZ)NO] and [(MTZ)AgNO]. The compound [(MTZ)AgNO] was three-fold more toxic to the A375 cells than the reference (cisplatin) and 15 times more cytotoxic against the A375 cells than the normal BJ cells. Complexes of metronidazole with Ag(I) are considered biocompatible at a concentration below 50 µmol/L.
Topics: Humans; Melanoma; Miconazole; Silver; Antineoplastic Agents; Metronidazole; Cell Line, Tumor; Coordination Complexes; Cell Survival; Skin Neoplasms
PubMed: 38791121
DOI: 10.3390/ijms25105081 -
Antibiotics (Basel, Switzerland) May 2024(1) Background: Although accounts for the majority of fungal infections, therapeutic options are limited and require alternative antifungal agents with new targets; (2)...
(1) Background: Although accounts for the majority of fungal infections, therapeutic options are limited and require alternative antifungal agents with new targets; (2) Methods: A biofilm formation assay with RPMI1640 medium was performed with extract. A combination antifungal assay, dimorphic transition assay, and adhesion assay were performed under the biofilm formation condition to determine the anti-biofilm formation effect. qRT-PCR analysis was accomplished to confirm changes in gene expression; (3) Results: extract significantly reduces biofilm formation by 51.65% at 1.56 μg/mL use and therefore increases susceptibility to miconazole. extract also inhibited the dimorphic transition of Candida; nearly 50% of the transition was inhibited when 1.56 μg/mL of the extract was treated. The extract of inhibited the expression of genes related to hyphal development and extracellular matrix of 34.4% and 36.0%, respectively, as well as genes within the Ras1-cAMP-PKA, Cph2-Tec1, and MAP kinase signaling pathways of 25.58%, 7.1% and 15.8%, respectively, at 1.56 μg/mL of extract treatment; (4) Conclusions: extract significantly reduced Candida biofilm formation, which lead to induced antifungal susceptibility to miconazole. It suggests that extract is a promising anti-biofilm candidate of since the biofilm formation of is an excellent target for candidiasis regulation.
PubMed: 38786162
DOI: 10.3390/antibiotics13050434 -
Pakistan Journal of Pharmaceutical... Jan 2024Hydrophilic drugs could be incorporated into the skin surface by manes of Lipogel. This study aimed to prepare miconazole lipogel with natural ingredients to enhance...
Hydrophilic drugs could be incorporated into the skin surface by manes of Lipogel. This study aimed to prepare miconazole lipogel with natural ingredients to enhance drug permeability using dimethyl Sulfoxide (DMSO). The miconazole lipogels, A1 (without DMSO) and A2 (with DMSO) were formulated and evaluated for organoleptic evaluation, pH, viscosity, stability studies, freeze-thawing, drug release profile and drug permeation enhancement. Results had stated that prepared lipogel's pH falls within the acceptable range required for topical delivery (4 to 6) while both formulations show good results in organoleptic evaluation. The A2 formulation containing DMSO shows better permeation of miconazole (84.76%) on the artificial skin membrane as compared to A1 lipogel formulation (50.64%). In in-vitro drug release studies, A2 for-mulation showed 87.48% drug release while A1 showed just 60.1% drug release from lipogel. Stability studies were performed on model formulations under environmental conditions and both showed good spreadibility, stable pH, free of grittiness and good consistency in formulation. The results concluded that A2 formulation containing DMSO shows better results as compared to DMSO-free drug lipogel.
Topics: Miconazole; Gels; Dimethyl Sulfoxide; Permeability; Drug Liberation; Viscosity; Drug Stability; Hydrogen-Ion Concentration; Skin Absorption; Chemistry, Pharmaceutical; Drug Compounding; Antifungal Agents; Administration, Cutaneous
PubMed: 38741405
DOI: No ID Found -
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 -
The Journal of Antibiotics Jul 2024Antibiotic resistance is a major health problem worldwide. Pseudomonas aeruginosa is a Gram-negative pathogen with an arsenal of virulence factors and elevated...
Antibiotic resistance is a major health problem worldwide. Pseudomonas aeruginosa is a Gram-negative pathogen with an arsenal of virulence factors and elevated antimicrobial resistance. It is a leading cause of nosocomial infections with high morbidity and mortality. The significant time and effort required to develop new antibiotics can be circumvented using alternative therapeutic strategies, including anti-virulence targets. This study aimed to investigate the anti-virulence activity of the FDA-approved drugs miconazole and phenothiazine against P. aeruginosa. The phenotypic effect of sub-inhibitory concentrations of miconazole and phenothiazine on biofilm, pyocyanin, protease, rhamnolipid and hemolysin activities in PAO1 strain was examined. qRT-PCR was used to assess the effect of drugs on quorum-sensing genes that regulate virulence. Further, the anti-virulence potential of miconazole and phenothiazine was evaluated in silico and in vivo. Miconazole showed significant inhibition of Pseudomonas virulence by reducing biofilm-formation approximately 45-48%, hemolytic-activity by 59%, pyocyanin-production by 47-49%, rhamnolipid-activity by approximately 42-47% and protease activity by 36-40%. While, phenothiazine showed lower anti-virulence activity, it inhibited biofilm (31-35%), pyocyanin (37-39%), protease (32-40%), rhamnolipid (35-40%) and hemolytic activity (47-56%). Similarly, there was significantly reduced expression of RhlR, PqsR, LasI and LasR following treatment with miconazole, but less so with phenothiazine. In-silico analysis revealed that miconazole had higher binding affinity than phenothiazine to LasR, RhlR, and PqsR QS-proteins. Furthermore, there was 100% survival in mice injected with PAO1 treated with miconazole. In conclusion, miconazole and phenothiazine are promising anti-virulence agents for P. aeruginosa.
Topics: Pseudomonas aeruginosa; Quorum Sensing; Miconazole; Phenothiazines; Biofilms; Virulence; Anti-Bacterial Agents; Animals; Microbial Sensitivity Tests; Pyocyanine; Pseudomonas Infections; Virulence Factors; Mice; Molecular Docking Simulation; Glycolipids
PubMed: 38724627
DOI: 10.1038/s41429-024-00731-5 -
Acta Tropica Jul 2024The surge in domestic cat adoption across India, particularly the rising preference for high-pedigree cats, coupled with environmental factors, has resulted in increased...
The surge in domestic cat adoption across India, particularly the rising preference for high-pedigree cats, coupled with environmental factors, has resulted in increased incidence of dermatophytosis among feline companions. Despite this growing concern, there is a noticeable scarcity of studies in India delving into the etiological factors contributing to dermatophytosis in cats. This disease is a threat to animal health and carries public health significance, given that cats are recognized reservoir hosts for Microsporum canis, a common dermatophyte affecting humans and animals. This study endeavours to identify the dermatophytes affecting cats and establish a standardized therapeutic regimen while accounting for the local stigma surrounding the regular bathing of cats. The study involved the examination of 82 cats presenting dermatological lesions, when subjected to cultural examination in dermatophyte test medium revealed 36 afflicted with dermatophytes. Isolates were presumptively identified by staining using lactophenol cotton blue, Chicago sky blue 6B, and Calcofluor white stains. Molecular-level identification of the isolates was confirmed through PCR-RFLP, amplifying the Internal Transcribed Spacer Sequence of 16 s rDNA, followed by restriction digestion using the Mva1 enzyme. Among the thirty-six isolates, 29 were identified as M. canis, while the remaining 7 were M. gypseum. The cases were categorized into five groups and treated with Lime Sulphur dip, 4 % chlorhexidine shampoo, a shampoo containing 2 % miconazole and 4 % chlorhexidine, oral itraconazole alone, and a combination of oral itraconazole with lime-Sulphur dip. Statistical analysis revealed that the response was notably swifter with lime Sulphur dip when considering only topical therapy. Moreover, the mycological cure was most expeditious when combining Lime Sulphur dip with oral itraconazole. These findings underscore the pivotal role of topical biocides in feline dermatophytosis treatment, potentially reducing the reliance on specific antifungals and thereby contributing to the mitigation of antimicrobial resistance emergence.
Topics: Cats; Animals; Cat Diseases; India; Tinea; Antifungal Agents; Microsporum; Male; Female; Arthrodermataceae; Itraconazole; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; DNA, Fungal; DNA, Ribosomal Spacer
PubMed: 38723739
DOI: 10.1016/j.actatropica.2024.107237 -
Acta Dermatovenerologica Alpina,... Jun 2024Hailey‒Hailey disease is a rare chronic autosomal-dominant blistering disease characterized by erosions, fissures, and vegetations occurring in intertriginous regions....
Hailey‒Hailey disease is a rare chronic autosomal-dominant blistering disease characterized by erosions, fissures, and vegetations occurring in intertriginous regions. To date, there is no specific treatment and there are no therapeutic guidelines, which makes management of the disease challenging. We present the case of a 43-year-old man unsuccessfully treated for Hailey‒Hailey disease with topical and systemic corticosteroids, antibiotics, and surgical debridement. At presentation he had erosions, vegetations, and infection in the axillae and groin. We introduced oral methotrexate, 10 mg weekly, and complete remission was achieved in 3 weeks. After 8 weeks, we decided to discontinue methotrexate due to lesion absence. Over 3 years of follow-up, mild flares were effectively managed with topical miconazole or mild steroid creams. We conclude that oral methotrexate is safe and effective for achieving long-term remission in Hailey‒Hailey disease.
Topics: Humans; Pemphigus, Benign Familial; Male; Adult; Methotrexate; Administration, Oral; Dermatologic Agents; Immunosuppressive Agents; Treatment Outcome
PubMed: 38708770
DOI: No ID Found -
BMJ Open May 2024To evaluate the efficacy of topical miconazole or amorolfine compared to placebo for mild to moderately severe onychomycosis. (Randomized Controlled Trial)
Randomized Controlled Trial
How effective is topical miconazole or amorolfine for mild to moderately severe onychomycosis in primary care: the Onycho Trial - a randomised double-blind placebo-controlled trial.
OBJECTIVES
To evaluate the efficacy of topical miconazole or amorolfine compared to placebo for mild to moderately severe onychomycosis.
DESIGN
Randomised, double-blind, placebo-controlled trial, with computer-generated treatment allocation at a 1:1:1 ratio.
SETTING
Primary care, recruitment from February 2020 to August 2022.
PARTICIPANTS
193 patients with suspected mild to moderately severe onychomycosis were recruited via general practices and from the general public, 111 of whom met the study criteria. The mean age of participants was 51 (SD 13.1), 51% were female and onychomycosis was moderately severe (mean OSI 12.1 (SD 8.0)).
INTERVENTIONS
Once-daily miconazole 20 mg/g or once-weekly amorolfine 5% nail lacquer solution was compared with placebo (denatonium benzoate solution).
MAIN OUTCOME MEASURES
Complete, clinical and mycological cure at 6 months. Secondary outcomes were clinical improvement, symptom burden, quality of life, adverse effects, compliance, patient-perceived improvement and treatment acceptability.
RESULTS
Based on intention-to-treat analysis, none of the participants receiving miconazole or amorolfine reached complete cure compared with two in the placebo group (OR not estimable (n.e.), p=0.493 and OR n.e., p=0.240, respectively). There was no evidence of a significant difference between groups regarding clinical cure (OR n.e., p=0.493 and OR 0.47, 95% CI 0.04 to 5.45, p=0.615) while miconazole and amorolfine were less effective than placebo at reaching both mycological cure (OR 0.25, 95% CI 0.06 to 0.98, p=0.037 and OR 0.23, 95% CI 0.06 to 0.92, p=0.029, respectively) and clinical improvement (OR 0.26, 95% CI 0.08 to 0.91, p=0.028 and OR 0.25, 95% CI 0.07 to 0.85, p=0.021, respectively). There was no evidence of a significant difference in disease burden, quality of life, adverse reactions, compliance, patient-perceived improvement or treatment acceptability.
CONCLUSIONS
Topical miconazole and amorolfine were not effective in achieving a complete, clinical or mycological cure of mild to moderately severe onychomycosis, nor did they significantly alleviate the severity or symptom burden. These treatments should, therefore, not be advised as monotherapy to treat onychomycosis.
TRIAL REGISTRATION NUMBER
WHO ICTRP NL8193.
Topics: Humans; Miconazole; Onychomycosis; Female; Double-Blind Method; Male; Middle Aged; Antifungal Agents; Administration, Topical; Treatment Outcome; Adult; Primary Health Care; Quality of Life; Aged; Severity of Illness Index; Morpholines
PubMed: 38702077
DOI: 10.1136/bmjopen-2023-081914 -
ACS Applied Bio Materials May 2024Carbon dots (CDs) were synthesized hydrothermally by mixing citric acid (CA) and an antifolic agent, sulfanilamide (SNM), employed for pH sensing and bacterial growth...
Carbon dots (CDs) were synthesized hydrothermally by mixing citric acid (CA) and an antifolic agent, sulfanilamide (SNM), employed for pH sensing and bacterial growth inactivation. Sulfanilamide is a prodrug; aromatic hetero cyclization of the amine moiety along with other chemical modifications produces an active pharmacological compound (chloromycetin and miconazole), mostly administered for the treatment of various microbial infections. On the other hand, the efficacy of the sulfanilamide molecule as a drug for antimicrobial activity was very low. We anticipated that the binding of the sulfanilamide molecule on the carbon dot (CD) surface may form antibacterial CDs. Citric acid was hybridized with sulfanilamide during the hydrothermal preparation of the CDs. The molecular fragments of bioactivated sulfanilamide molecule play a crucial role in bacterial growth inactivation for Gram-positive and Gram-negative bacteria. The functional groups of citric acid and sulfanilamide were conserved during the CD formation, facilitating the zwitterionic behavior of CDs associated with its photophysical activity. At low concentrations of CDs, the antibacterial activity was apparent for Gram-positive bacteria only. This Gram-positive bacteria selectivity was also rationalized by zeta potential measurement.
Topics: Carbon; Anti-Bacterial Agents; Hydrogen-Ion Concentration; Sulfanilamide; Microbial Sensitivity Tests; Particle Size; Biocompatible Materials; Materials Testing; Quantum Dots; Sulfanilamides; Gram-Positive Bacteria; Gram-Negative Bacteria
PubMed: 38662509
DOI: 10.1021/acsabm.3c01130