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This review examined the current state of knowledge on the modifications of commercial soft lining materials (SLMs) with a variety of antifungal compounds: (i) polyene antibiotics, including nystatin and amphotericin B, (ii) azole drugs, including fluconazole, itraconazole, clotrimazole, ketoconazole, and miconazole, and (iii) antiseptics, including chlorhexidine salts to give them anti-Candida albicans properties. The effect of such modifications on the SLMs' physical properties, such as drug release, water sorption, surface properties, bond strength, tensile strength, and hardness, was also analyzed. In effect, this study provided a unique compilation of research results obtained for numerous properties of SLM modified with antifungal compounds that differ in their chemical structure and mechanism of antifungal action. These results might also be useful for prosthetic dentistry, where SLMs are used to prevent and treat candidiasis, the most common disease among denture wearers. [ABSTRACT FROM AUTHOR]

Introduction A rise in tinea cruris among Thai Naval Cadets has been observed. Clotrimazole powder has been shown to be effective as an adjunct treatment for tinea cruris; however, its efficacy as a monotherapy is limited. Objectives The aim is to determine the efficacy of 1% clotrimazole cream versus 1% clotrimazole powder in treating tinea cruris. Material and Methods A randomized trial was conducted at the Thai Naval Rating School, Chonburi, Thailand. Naval rating cadets with suspected tinea cruris were randomly assigned to one of two groups: 1% clotrimazole cream or 1% clotrimazole powder, and they were instructed to apply the related medication to the affected lesion twice daily for 4 weeks. Clinical and symptomatic evaluations were carried out at 4 and 8 weeks. Results All 17 and 14 participants who received 1% clotrimazole cream and powder, respectively, were included. After 4 weeks, the clinical cure rates were 76.5% in the cream group and 85.7% in the powder group (P  = .664). All participants were clinically cured within 8 weeks. The self-evaluation of itch severity using a visual analog scale (VAS) revealed no significant difference between the two groups (P  = .343). The dermatology quality of life index decreased as clinical improvement was achieved in both the clotrimazole cream and powder groups (6.0 vs. 7.5 score reductions, respectively; P  = .765). The score for sweat reduction was higher in the 1% clotrimazole powder group compared to the cream group (5.0 vs. 4.0, respectively; P  = .006). Conclusion Monotherapy with 1% clotrimazole powder showed comparable efficacy to 1% clotrimazole cream. Furthermore, the powder treatment reduced sweat more effectively compared to the cream. [ABSTRACT FROM AUTHOR]

Objective • To evaluate the impact of clotrimazole suppositories on the distribution of vaginal pathogens and oxidative stress in patients with vaginitis. Methods • A total of 120 patients with vaginitis were recruited from our hospital between January 2021 and December 2022 and were divided into an observation group and a control group using a random envelope method. The control group received treatment with miconazole tablets alone, while the observation group received combined treatment with miconazole tablets and clotrimazole suppositories. Vaginal secretions were collected from the subjects for pathogenic microbial testing. The clinical efficacy of the patients was evaluated, and indicators related to vaginal microecology and microbial imbalance were examined. Serum levels of IL-8, CRP, TNF-α, IL-6, PCT, P, LH, FSH, SOD, MDA, NO, and ET-1 were measured in the subjects. Results • Among patients with vaginitis, bacteria, fungi, and gram-negative cocci accounted for a relatively high proportion, with bacterial infections accounting for more than 30% and fungal and gram-negative cocci infections both exceeding 10%. Pathogenic infections such as Chlamydia and Trichomonas were less than 10%. The observation group showed significantly higher clinical efficacy compared to the control group, with a statistically significant difference (P < .05). Following treatment, the observation group exhibited significantly lower scores for itching, vaginal discharge, and burning sensation compared to the control group, with a statistically significant difference (P < .05). After treatment, the observation group had significantly lower bacterial density and Nugent score, higher cleanliness, positive lactobacilli rate, and pH value compared to the control group, and the difference was statistically significant (P < .05). After treatment, the observation group demonstrated significantly lower blood levels of IL-8, CRP, TNF-α, IL-6, and PCT compared to the control group, with a statistical significance of P < .05. Similarly, the levels of P, LH, and FSH hormones in the observation group were significantly lower than those in the control group, also with a statistical significance of P < .05. In contrast, the levels of SOD and NO in the observation group were significantly higher, while the levels of MDA and ET-1 were significantly lower compared to the control group, with a statistical significance of P < .05. Conclusion • Clotrimazole suppositories have been shown to significantly enhance therapeutic outcomes for patients with vaginitis by alleviating inflammation, rebalancing vaginal microecology, regulating hormone secretion, and mitigating oxidative stress. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidiasis (VVC) alters the innate cervicovaginal immunity, which provides an important barrier against viruses and other infections. The incidence of this disease has not decreased in the last 30 years, so effective treatments are still needed. Nanoparticles (NPs) of cellulose acetate phthalate (CAP) and clotrimazole (CLZ) were prepared by the emulsification-diffusion method. NPs were characterized using dynamic light scattering, atomic force microscopy and differential scanning calorimetry; their release profile was determined by the dialysis bag technique and mucoadhesion was evaluated with the mucin-particle method. The growth inhibition study of Candida albicans was carried out using the plate counting technique. Finally, accelerated physical stability tests of NPs were carried out, both in water and in SVF. The CAP-CLZ NPs had an average diameter of 273.4 nm, a PDI of 0.284, smooth surfaces and spherical shapes. In vitro release of CLZ from the CAP NPs was categorized with the Weibull model as a matrix system in which initial release was rapid and subsequently sustained. The inhibition of C. albicans growth by the CAP-CLZ NPs was greater than that of free CLZ, and the CAP-only NPs had a microbicidal effect on C. albicans. The NPs showed poor mucoadhesiveness, which could lead to studies of their mucopenetration capacities. An accelerated physical stability test revealed the erosion of CAP in aqueous media. A nanoparticulate system was developed and provided sustained release of CLZ, and it combined an antifungal agent with a microbial polymer that exhibited antifungal activity against C. albicans. [ABSTRACT FROM AUTHOR]

Clotrimazole (CLZ), traditionally an antifungal agent, unveils promising avenues in cancer therapy, particularly in addressing bladder and prostate cancers. In vitro assessments underscore its remarkable efficacy as a standalone treatment, significantly diminishing cancer cell viability. Mechanistically, CLZ operates through multifaceted pathways, including the inhibition of Ca2+-dependent K+ channels, suppression of glycolysis-related enzymes, and modulation of the ERK-p65 signaling cascade, thus underscoring its potential as a versatile therapeutic agent. Our investigation sheds light on intriguing observations regarding the resilience of UM-UC-5 bladder cancer cells against high doses of paclitaxel (PTX), potentially attributed to heightened levels of the apoptosis-regulating protein Mcl-1. However, synergistic studies demonstrate that the combination of Doxorubicin (DOXO) and CLZ emerges as particularly potent, especially in prostate cancer contexts. This effectiveness could be associated with the inhibition of drug efflux mediated by multidrug resistance-associated protein 1 (MRP1), underscoring the importance of exploring combination therapies in cancer treatment paradigms. In essence, our findings shed light on the anticancer potential of CLZ, emphasizing the significance of tailored approaches considering specific cancer types and molecular pathways in drug repurposing endeavors. While further validation and clinical exploration are warranted, the insights gleaned from this study offer promising prospects for enhancing cancer therapy efficacy. [ABSTRACT FROM AUTHOR]

To compare the efficacy of gel foam-soaked pyodine with a single topical application of clotrimazole ointment in the treatment of otomycosis. This randomized controlled trial included 90 patients who presented to ENT OPD with complaints of earache, watery ear discharge, pruritis, and ear blockage and were clinically diagnosed as a case of otomycosis via otoscopy. The external auditory canal of the patient was cleared of fungal debris via suction before treatment. In Group A, the ear canal was filled with 1% clotrimazole ointment by using an IV catheter and syringe and in Group B 10% pyodine-soaked gel foam was placed in the external auditory canal. The patients were followed up on post-treatment days 7 and 14. The results showed that out of 90 patients with otomycosis, the left ear was affected in 50(55.6%) patients and the right ear in 40(44.4%). 8(8.9%) of 90 patients had controlled preexisting diabetes mellitus. On the 7th post-treatment follow-up day, 17 (41.5%) patients in Group A and 28(66.7%) patients in Group B showed no fungal spores. Other symptom resolution was also comparable in both groups. At the 14th day follow-up 33(80.5%) patients in Group A and 38(92.7% patients in Group B showed no fungal hyphae on otoscopy. In terms of treatment response 19(46.34%) patients in Group A and 21(51.21%) patients in Group B showed good treatment response at the end of 2nd post-treatment week with a p-value of 0.798. yodine-soaked gel foam placement in the external auditory canal is a safe and effective method for the treatment of otomycosis with the efficiency of this method comparable to a single topical clotrimazole ointment application. [ABSTRACT FROM AUTHOR]

Background/objectives: Topically applied antifungal agents can induce adverse effects, such as pain and irritation. The transient receptor potential (TRP) channels—TRPA1 and TRPV1—mainly expressed in sensory neurons, act as sensors for detecting irritants. This study aims to evaluate the involvement of nociceptive channels in topical antifungal‐induced pain and irritation. We tested nine topical antifungals belonging five classes: isoconazole, econazole, miconazole, clotrimazole, and ketoconazole as imidazoles; liranaftate as a thiocarbamate; terbinafine as an allylamine; amorolfine as a morpholine; and butenafine as a benzylamine. Methods: Intracellular calcium concentrations ([Ca2+]i) and membrane currents in response to antifungals were measured to estimate channel activity using heterologously expressing cells and isolated mouse sensory neurons. Results: In mouse TRPA1‐expressing cells, all the tested drugs induced an increase in [Ca2+]i, which was abrogated or reduced by a TRPA1 blocker. Although many drugs evoked the TRPA1‐nonspecific [Ca2+]i response at high concentrations, responses to clotrimazole, ketoconazole, and liranaftate were TRPA1 specific and elicited current responses in TRPA1‐expressing cells. In mouse TRPV1‐expressing cells, clotrimazole and ketoconazole elicited [Ca2+]i and current responses. In mouse sensory neurons, liranaftate‐induced increase in [Ca2+]i was abrogated by a TRPA1 blocker and Trpa1 deletion. Responses to ketoconazole were inhibited by TRPA1 and TRPV1 blockers and by the genetic deletion of either channel. Conclusion: These results suggest that topical antifungal‐induced pain and irritation are attributable to the activation of nociceptive TRPA1 and/or TRPV1 channel/s. Consequently, caution should be exercised in the use of topical antifungals with symptoms of pain. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidiasis (VVC) is a prevalent gynecological infection characterized by high incidence and recurrent episodes, causing significant distress in women. This study aims to assess the effectiveness of different clotrimazole and fluconazole treatment regimens for severe vulvovaginal candidiasis (SVVC). A retrospective analysis was conducted on 1303 cases of SVVC among first-time visitors to the gynecology outpatient department at Peking University Shenzhen Hospital between January 2013 and December 2022. Vaginal secretions were systematically collected for fungal culture, with species identification conducted using Chromogenic culture medium and API Candida test reagents. Mycological cure rates were assessed at days 7–14, days 25–35, and day 35 to 6 months after treatment. The three-dose clotrimazole regimen demonstrated significantly higher mycological cure rates (85.7%, 80.0% and 74.6% at three follow-up periods, respectively) compared to the two-dose clotrimazole regimen (76.0%, 61.6%, and 59.8%, all P < 0.05). The three-dose fluconazole regimen showed no significant difference to three-dose clotrimazole regimen, with cure rates of 82.8%, 79.3%, and 75.9% (all P > 0.05). The two-dose fluconazole regimen had cure rates of 74.3%, 56.4% and 51.1%, with no significant difference from two-dose clotrimazole regimen at days 7–14 and 25–35, but lower than three-dose fluconazole regimen at days 25–35 and 35 to 6 months. The three-dose clotrimazole regimen demonstrated higher cure rates in Candida albicans and non-albicans Candida SVVC cases than two-dose regimen. These findings suggest that three-dose antifungal regimens may be more efficacious than two-dose regimens for SVVC. The three-dose clotrimazole regimen could serve as a promising alternative for SVVC management. [ABSTRACT FROM AUTHOR]

Abstract Patients with multiple myeloma (MM) experience relapse and drug resistance; therefore, novel treatments are essential. Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ’s effects on MM are unclear. We investigated CTZ’s effect on MM cell proliferation and apoptosis induction mechanisms. CTZ’s effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-κB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-IκBα. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0/G1 arrest, inhibiting the NF-κB pathway, and has the potential for treating MM.

Clotrimazole (CLZ), traditionally an antifungal agent, unveils promising avenues in cancer therapy, particularly in addressing bladder and prostate cancers. In vitro assessments underscore its remarkable efficacy as a standalone treatment, significantly diminishing cancer cell viability. Mechanistically, CLZ operates through multifaceted pathways, including the inhibition of Ca2+-dependent K+ channels, suppression of glycolysis-related enzymes, and modulation of the ERK-p65 signaling cascade, thus underscoring its potential as a versatile therapeutic agent. Our investigation sheds light on intriguing observations regarding the resilience of UM-UC-5 bladder cancer cells against high doses of paclitaxel (PTX), potentially attributed to heightened levels of the apoptosis-regulating protein Mcl-1. However, synergistic studies demonstrate that the combination of Doxorubicin (DOXO) and CLZ emerges as particularly potent, especially in prostate cancer contexts. This effectiveness could be associated with the inhibition of drug efflux mediated by multidrug resistance-associated protein 1 (MRP1), underscoring the importance of exploring combination therapies in cancer treatment paradigms. In essence, our findings shed light on the anticancer potential of CLZ, emphasizing the significance of tailored approaches considering specific cancer types and molecular pathways in drug repurposing endeavors. While further validation and clinical exploration are warranted, the insights gleaned from this study offer promising prospects for enhancing cancer therapy efficacy.

Background Objective Methods Results Conclusion Nakaseomyces glabratus (N. glabratus) formerly known as Candida glabrata (C. glabrata), is an endogenous opportunistic pathogen, which is generally located in the gastrointestinal tract but can spread in immunocompromised patients. N. glabratus is the second most common pathogen that causes candidemia in several countries. N. glabratus virulence factors may increase antifungal resistance and reduce the number of available treatment options. High resistance to azoles and increasing resistance to echinocandins have been previously reported in N. glabratus.To establish the distribution of N. glabratus isolates in Europe and its drug susceptibility/resistance in each country over the last 7 years.The search was performed across three databases: PubMed, Scopus and Scielo, using the MeSH terms: “Candida glabrata”, “Nakaseomyces glabratus”, “Europe”, “resistance” and “Epidemiology” exclusively in English. All available information from January 2002 to December 2022 was included, excluding reviews, meta‐analyses and book chapters.Fifty‐seven articles with information on antifungal susceptibility in Europe were retrieved and analysed with a total of 15,400 reported C. glabrata isolates. Remarkably, nations that presented the maximum number of cases during the study period included the United Kingdom (n = 7241, 47.02%), France (n = 3190, 20.71%), Spain (n = 900, 5.84%), Hungary (n = 745, 4.84%) and Italy (n = 486, 3.16%). C. glabrata isolates presented resistance to azoles [voriconazole (n = 2225, 14.45%), fluconazole (n = 1612, 10.47%), itraconazole (n = 337, 2.19%) and clotrimazole (n = 89, 0.58%)], increased resistance to echinocandins, especially to anidulafungin (n = 138, 0.89%), and high sensitivity to amphotericin B.The number of candidemia cases associated with triazole‐resistant N. glabratus isolates have been increasing in Europe. Therefore, echinocandins and amphotericin B can be considered optional empirical treatments; however, antifungal susceptibility testing is required to determine the best therapeutic options. [ABSTRACT FROM AUTHOR]

Background: The emergence of tolerance to antifungal agents in Candida albicans complicates the treatment of fungal infections. Understanding the mechanisms underlying this tolerance is crucial for developing effective therapeutic strategies. Objective: This study aims to elucidate the genetic and molecular basis of ketoconazole tolerance in C. albicans, focusing on the roles of chromosomal aneuploidy, Hsp90, and calcineurin. Methods: The wild-type C. albicans strain SC5314 was exposed to increasing concentrations of ketoconazole (0.015-32 µg/mL) to select for tolerant adaptors. Disk diffusion and spot assays were used to assess tolerance. Wholegenome sequencing identified chromosomal changes in the adaptors. The roles of Hsp90 and calcineurin in maintaining and developing ketoconazole tolerance were investigated using specific inhibitors and knockout strains. Results: Adaptors exhibited tolerance to ketoconazole concentrations up to 16 µg/mL, a significant increase from the parent strain's inhibition at 0.015 µg/mL. All tolerant adaptors showed amplification of chromosome R, with 29 adaptors having trisomy and one having tetrasomy. This aneuploidy was unstable, reverting to euploidy and losing tolerance in drug-free conditions. Both Hsp90 and calcineurin were essential for maintaining and developing ketoconazole tolerance. Inhibition of these proteins resulted in loss of tolerance. The efflux gene CDR1 was not required for the development of tolerance. Chromosome R trisomy and tetrasomy induce cross-tolerance to other azole antifungal agents, including clotrimazole and miconazole, but not to other antifungal classes, such as echinocandins and pyrimidines, exemplified by caspofungin and 5-flucytosine. Conclusion: Ketoconazole tolerance in C. albicans is mediated by chromosomal aneuploidy, specifically chromosome R amplification, and requires Hsp90 and calcineurin. These findings highlight potential targets for therapeutic intervention to combat antifungal tolerance and improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Background and Aim: Scopulariopsis brevicaulis (S. brevicaulis) is an opportunistic pathogen causing both localized and systemic infections. Recent studies indicated DNA sequence variation among S. brevicaulis isolates from different clinical sources. In this study we aimed to isolate and diagnose S. brevicaulis from nail and skin samples of diabetic patients and investigate their phylogenetic diversity based on the internal transcribed spacer 1 (ITS) sequencing. Materials and Methods: Fifty nail and skin samples were collected from diabetic patients suffering from skin lesions. Conventional diagnostic methods were utilized to identify the bacterial and fungal isolates. Fungal DNA was extracted and ITS 1 region was amplified by PCR and sequenced using Sanger method. Multiple sequence alignment and phylogenetic analysis were conducted using Clustal W and MEGA software. Finally, antifungal susceptibility test was performed by disc diffusion method. Results: Based on the culture, microscopic evaluation, and biochemical tests, various types of bacteria and fungi were isolated. Among 50 nail and skin samples, 25 fungal isolates (50%) and 5 bacterial isolates (10%) were recovered. Interestingly, one of the fungal isolates was identified as Scopulariopsis brevicaulis. This isolate was associated with a clinical case involving a 52-year-old male. Phylogenetic analysis of the ITS region showed our isolate (Scopulariopsis brevicaulis) closely matched and clustered in the same clade as those reported in the US, differing from those reported in Iraq (Basrah), Iran, and Turkey. Furthermore, our isolate exhibited a multi-drug resistance pattern against antifungal agents. Conclusion: This study highlights the importance of identifying S. brevicaulis in diabetic patients due to its multi-drug resistance. DNA sequencing and phylogenetic analysis revealed genetic divergence from the strains within the same country and other different countries. [ABSTRACT FROM AUTHOR]

Clotrimazole is a type of antifungal medication developed from azole compounds. It exhibits several biological actions linked to oxidative stress. This study focuses on the oxidative effects of clotrimazole on the eukaryotic model yeast, Saccharomyces cerevisiae. Our results showed that although initial nitric oxide levels were above control in clotrimazole exposed cells, they showed decreasing tendencies from the beginning of incubation and dropped below control at 125 µM from the 60th min. The highest superoxide anion and hydrogen peroxide levels were 1.95- and 2.85-folds of controls at 125 µM after 15 and 60 min, respectively. Hydroxyl radical levels slightly increased throughout the incubation period in all concentrations and reached 1.3-fold of control, similarly at 110 and 125 µM in the 90th min. The highest level of reactive oxygen species was observed at 110 µM, 2.31-fold of control. Although NADH/NADPH oxidase activities showed similar tendencies for all conditions, the highest activities were found as 3.07- and 2.27-folds of control at 125 and 110 µM in the 15th and 30th min, respectively. The highest superoxide dismutase and catalase activities were 1.59- and 1.21-folds of controls at 110 µM clotrimazole in 30 and 90 min, respectively. While the drug generally induced glutathione-related enzyme activities, the ratios of glutathione to oxidized glutathione were above the control only at low concentrations of the drug. The levels of lipid peroxidation in all treated cells were significantly higher than the controls. The findings crucially demonstrate that this medicine can generate serious oxidative stress in organisms.Highlights: Clotrimazole treatment enhanced NO• and ROS levels in S. cerevisiae cells. NADH and NADPH oxidases both cause and contribute to ROS generation. The activities of two major antioxidant enzymes, SOD and CAT, were also highly increased. The antioxidant system’s response was insufficient to keep LPO levels under control. [ABSTRACT FROM AUTHOR]

Over the past decades, comprehensive attempts have been made to improve physiological absorption by designing delivery systems, using suitable carriers, and altering the route of administration. Here, the vaginal route was targeted using capsular-shaped biodegradable in situ porous drug-eluting inserts (DEI) using clotrimazole as a model drug and PCL and PEO WSR 303 as rate-controlling polymers. Morphology, thermal properties, and degradation kinetics were assessed in comparison to non-porous DEI. The optimized DEI showed site-specific controlled drug release as per disease need, which may lead to enhanced bioavailability as well as patient compliance with reduced dose-related side effects. [ABSTRACT FROM AUTHOR]

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Clotrimazole (CMZ) is a classical antifungal drug for studying crystallization. In this study, a new CMZ polymorph (Form 2) was discovered during the process of nucleation and growth rate determination in the melt. High-quality single crystals were grown from melt microdroplets to determine the crystal structure by x-ray diffraction. Form 2 is metastable and exhibits a disordered structure. The crystal nucleation and growth kinetics of the two CMZ polymorphs were systematically measured. Form 2 nucleates and grows faster than the existing form (Form 1). The maximum nucleation rate of Forms 1 and 2 was observed at 50 °C (1.07 Tg). The summary of the maximum nucleation rate temperature of CMZ and the other six organic compounds indicates that nucleation near Tg in the supercooled liquid is a useful approach to discovering new polymorphs. This study is relevant for the discovering new drug polymorphs through an understanding of nucleation and growth kinetics during melt crystallization. [ABSTRACT FROM AUTHOR]

Abstract Background Vaginal candidiasis (VC) commonly affects pregnant women. Traditionally, clotrimazole vaginal tablets (CLO) have been the cornerstone of management. However, sertaconazole ovules (SER) offer a novel topical antimycotic option. This double-blinded, randomized trial evaluated the efficacy of single-dose SER and CLO in treating acute VC during pregnancy. Methods From June 2020 to May 2021, this trial recruited pregnant women aged ≥ 18 years with VC symptoms (abnormal vaginal discharge and/or vulvar/vaginal itching) confirmed by microscopy. Participants with ≥ 4 VC episodes in the prior year, immunocompromised status, or imidazole contraindications and those who were absent at the 2-week follow-up were excluded. Participants were randomized to receive either 300 mg SER or 500 mg CLO. Evaluations 2 weeks after the initial medication administration included clinical cure (self-reported resolution of all symptoms), microscopic cure (pseudohyphal absence), patient satisfaction, side effects, and time to clinical cure. Participants with persistent VC received weekly SER doses until delivery. Assessments of recurrence and pregnancy outcomes were done. Results The analysis included 96 participants (48 per group, mean age 27.4 ± 7.4 years, gestational age at diagnosis 22.9 ± 6.4 weeks). Without statistical significance, SER achieved a higher clinical cure rate (62.5% vs 50%, p = 0.217; a mean difference of 12.5%, 95%CI: -17.5% to 42.5%; and a rate ratio of 1.25, 95%CI: 0.71 to 2.23) and a lower microscopic cure (47.9% vs. 62.5%, p = 0.151; a mean difference of -14.6%, 95%CI: -44.3% to 15.1%; and a rate ratio of 0.77, 95%CI: 0.43 to 1.37). The two groups had comparable times to clinical cure (SER: 3.1 ± 1.8 days, CLO: 3.4 ± 2.7 days; p = 0.848) and substantial satisfaction rates (SER: 66.7%, CLO: 60.4%; p = 0.753). No side effects were reported. Of 60 participants who gave birth at Siriraj Hospital, there were no significant differences in pregnancy outcomes. Repeated SER dosing eradicated symptoms and enhanced the microscopic cure rate. Recurrence was observed in four SER and two CLO participants within 1–2 months. Conclusion In the treatment of acute VC during pregnancy, 300 mg SER and 500 mg CLO exhibited comparable efficacy in terms of clinical and microscopic cure rates, satisfaction, side effects, time to clinical cure, recurrence rates, and pregnancy outcomes. Trial registration TCTR20190308004 (registration date March 8, 2019).

Miconazole is an antimycotic drug showing anti-cancer effects in several cancers. However, little is known on its effects in melanoma. A375 and SK-MEL-28 human melanoma cell lines were exposed to miconazole and clotrimazole (up to 100 mM). Proliferation, viability with MTT assay and vascular mimicry were assayed at 24 h treatment. Molecular effects were measured at 6 h, namely, ATP-, ROS-release and mitochondria-related cytofluorescence. A metabolomic profile was also investigated at 6 h treatment. Carnitine was one of the most affected metabolites; therefore, the expression of 29 genes involved in carnitine metabolism was investigated in the public platform GEPIA2 on 461 melanoma patients and 558 controls. After 24 h treatments, miconazole and clotrimazole strongly and significantly inhibited proliferation in the presence of 10% serum on either melanoma cell lines; they also strongly reduced viability and vascular mimicry. After 6 h treatment, ATP reduction and ROS increase were observed, as well as a significant reduction in mitochondria-related fluorescence. Further, in A375, miconazole strongly and significantly altered expression of several metabolites including carnitines, phosphatidyl-cholines, all amino acids and several other small molecules, mostly metabolized in mitochondria. The expression of 12 genes involved in carnitine metabolism was found significantly modified in melanoma patients, 6 showing a significant impact on patients' survival. Finally, miconazole antiproliferation activity on A375 was found completely abrogated in the presence of carnitine, supporting a specific role of carnitine in melanoma protection toward miconazole effect, and was significantly reversed in the presence of caspases inhibitors such as ZVAD-FMK and Ac-DEVD-CHO, and a clear pro-apoptotic effect was observed in miconazole-treated cells, by FACS analysis of Annexin V-FITC stained cells. Miconazole strongly affects proliferation and other biological features in two human melanoma cell lines, as well as mitochondria-related functions such as ATP- and ROS-release, and the expression of several metabolites is largely dependent on mitochondria function. Miconazole, likely acting via carnitine and mitochondria-dependent apoptosis, is therefore suggested as a candidate for further investigations in melanoma treatments. [ABSTRACT FROM AUTHOR]

Mycoses of the skin are infectious diseases caused by fungal microorganisms that are generally treated with topical agents. However, such therapy is often ineffective and has to be supported by oral use of active substances, which, in turn, can cause many side effects. A good alternative for the treatment of deep-skin mycoses seems to be microneedles (MNs). The aim of this research was to fabricate and evaluate the properties of innovative MNs coated with a hydrogel as potential carriers for clotrimazole (CLO) in the treatment of deep fungal skin infections. A 3D printing technique using a photo-curable resin was employed to produce MNs, which were coated with hydrogels using a dip-coating method. Hydrogels were prepared with carbopol EZ-3 Polymer (Lubrizol) in addition to glycerol and triisopropanolamine. Clotrimazole was introduced into the gel as the solution in ethanol or was suspended. In the first step of the investigation, a texture analysis of hydrogels was prepared with a texture analyzer, and the drug release studies were conducted with the use of automatic Franz diffusion cells. Next, the release profiles of CLO for coated MNs were checked. The last part of the investigation was the evaluation of the antifungal activity of the prepared systems, and the inhibition of the growth of Candida albicans was checked with the diffusion and suspended-plate methods. The texture profile analysis (TPA) for the tested hydrogels showed that the addition of ethanol significantly affects the following studied parameters: hardness, adhesiveness and gumminess, causing a decrease in their values. On the other hand, for the gels with suspended CLO, better spreadability was seen compared to gels with dissolved CLO. The presence of the active substance did not significantly affect the values of the tested parameters. In the dissolution study, the results showed that higher amounts of CLO were released for MNs coated with a hydrogel containing dissolved CLO. Also, microbiological tests proved its efficacy against fungal cultures. Qualitative tests carried out using the diffusion method showed that circular zones of inhibition of fungal growth on the plate were obtained, confirming the hypothesis of effectiveness. The suspension-plate technique confirmed the inhibitory effect of applied CLO on the growth of Candida albicans. From the analysis of the data, the MNs coated with CLO dissolved in hydrogel showed better antifungal activity. All received results seem to be helpful in developing further studies for MNs as carriers of antifungal substances. [ABSTRACT FROM AUTHOR]

Creams are among the most analytically challenging dosage forms both in product analysis and in cleaning validation. This is especially true when highly lipophilic drugs are the active ingredients. The case is getting more challenging with the greenness emerges as an evaluation criterion where solvents and wastes should be minimized. Green methods are difficult to achieve with lipophilic drugs and creams that may encounter high carry-over tendency. In this study, an ecofriendly RP-HPLC-DAD method was developed for the determination of hydrocortisone acetate (HCA), mometasone furoate (MOM), betamethasone valerate (BTM), clotrimazole (CLT) and oxytetracycline (OXT) in the presence of miconazole as examples of lipophilic drugs commonly formulated in creams. The separation was performed on a C18 (5 µm, 150 × 4.6 mm ID) column using methanol–water (80 : 20, v/v) as a mobile phase and a photo-diode array detector. The method was validated according to ICH guidelines. Greenness and whiteness were assessed by NEMI, GAPI, AGREE, Eco-scale, and the RGB 12 model and compared to currently available methods. The developed method was found linear with r2 > 0.99 within the range of 0.05–9.00 HCA, 0.1–9.0 MOM, 0.2–9.0 BTM, 0.6–9.0 CLT, and 5.0–9.0 µg/mL OXT. The accuracy (98.4 ± 1.7)–(102.3 ± 1.5) and precision (CV < 10%) were in acceptable ranges while retaining high sensitivity (LOD down to 15 ng). The proposed method proved to be environmentally friendly by applying different greenness and whiteness algorithms and was successfully applied to different cream formulations. In conclusion, the developed method outperforms currently available methods for the determination of tested lipophilic compounds in creams. [ABSTRACT FROM AUTHOR]

Vulvovaginitis is a prevalent gynaecological ailment worldwide, often attributed to bacteria, Candida fungi, or Trichomonas. The synergistic action of antifungal agents and essential oils can enhance the efficacy against pathogenic microorganisms. In this study, a simultaneous quantitative method for determining clotrimazole and eugenol in a laboratory-compounded gel product was developed using high-performance liquid chromatography with a photodiode array detector (HPLC-PDA). The HPLC-PDA system utilised in this study was the Shimadzu LC- 20AD, with a HiQ Sil RP C18 HS column (250 x 4.6 mm, 5 µm), and a mobile phase consisting of methanol-water in an 80:20 (v/v) ratio, employing isocratic elution at a flow rate of 1.0 ml/min. The injection volume was set at 20 µl, and detection was performed at a wavelength of 229.0 nm. The analytical procedure was validated in accordance with ASEAN guidelines for the validation of analytical procedures, successfully meeting the criteria for specificity, accuracy, system suitability, repeatability, intermediate precision, and linearity within the concentration range of 2.25 to 36.00 ppm for eugenol and 12.00 to 200.00 ppm for clotrimazole. Subsequently, this validated procedure was applied to quantify the clotrimazole and eugenol content in bulk materials and three different lots of gel products. The results for clotrimazole and eugenol content in both the raw materials and the gel product lots fell within an acceptable range, with deviations of less than ±10% compared to the labelled content.

The aim of this study was to prepare vaginal suppositories with mucoadhesive properties to prolong the action of antifungal component clotrimazole (CLO). This was achieved by preparing vaginal pessaries on a hydrophilic gel base composed of gelatin and gelatin enriched with PEG 400 (in a 1:1 ratio), and then checking the properties of the obtained vaginal drugs. The prepared globules, containing 100 mg of CLO, were characterized in terms of mass and swelling index, organoleptic analysis was also prepared. In addition, a texture analysis and a study of the dissolution of clotrimazole were performed. On the basis of the obtained results, it was concluded that the modification of the composition of the gelatin–glycerin base by the addition of macrogol had a positive effect on the mucoadhesive properties of the globules. In addition, due to the presence of PEG 400, the globules were stiffer. It was also observed that the presence of CLO reduces the value of the force needed for compression during the texture analysis study. Comparing the CLO release profiles of the prepared globules and commercially available clotrimazole tablets, the release profile for the globules was slower than for the tablets, which indicates the possibility of using mucoadhesive globules as a form of a drug that releases the medicinal substance more slowly at the site of administration.

Vaginal candidiasis poses significant health concerns that affect approximately 75% of women globally and often leads to discomfort and a decrease in quality of life. Traditional treatments, despite their effectiveness, may cause discomfort and adverse effects, such as vaginal discharge, bleeding, and dryness, promoting the exploration of alternative formulations. In this study, we aimed to develop a novel therapeutic approach for the treatment of vaginal candidiasis utilizing oleic acid containing emulgels made from thermoresponsive poloxamer-based hydrogels. These emulgels were designed to provide a sustained release of clotrimazole, an antifungal agent. Incorporating oleic acid enhanced the drug’s solubility and contributed to vaginal health. The formulations were characterized by their rheological properties, in vitro release, mucoadhesion, and spreadability. We conducted rheological measurements on the hydrogels that served as the base for the emulgels, as well as on the emulgels themselves. The emulgels exhibited continuous rheological behavior with changing temperatures, making them suitable for storage at room temperature. With an increasing HPMC content, we achieved enhanced mucoadhesion, which is beneficial for formulations used in body cavities. Moreover, in vitro release studies revealed sustained drug release profiles, which can be adjusted by varying the ratios of poloxamers and HPMC. These findings suggest that the developed emulgels offer a promising therapeutic option for vaginal candidiasis, addressing both the symptoms and the treatment of discomfort.

Background. Candidiasis is the common name for diseases caused by yeast of the genus Candida. Candida albicans is one of the most implicated species in superficial and invasive candidiasis. Antifungals, polyenes, and azoles have been used to treat candidiasis. However, due to the development of antifungal resistance, research of natural substances with potential antifungal effects at low concentrations or combined is also a possibility. Methods. The broth microdilution method was used to evaluate the antifungal activity. The biofilm formation was assessed using the microtiter plate method. The antibiofilm activities were assessed using micro plaque tetrazolium salt assay (MTT). The combination effect of antifungal with natural substances was made using the checkerboard method. Results. Among our isolates, clotrimazole was the most resistant, but amphotericin B was the most effective antifungal. The biofilm was formed by all isolates of C. albicans. Curcumin and piperine displayed antibiofilm activity with minimum biofilm inhibitory concentration (MBIC) and minimum eradicating concentration (MBEC) ranging from 64 to 1024 μg/mL and 256 to 2048 μg/mL. In combination, piperine presented double synergistic effects compared to curcumin with all antifungals tested. Curcumin shows more synergistic effect when combined with polyenes than with azoles. However, piperine shows a more synergistic effect when combined with azoles compared to polyenes. Conclusion. C. albicans was susceptible to curcumin and piperine both on planktonic cells and biofilm. The combination of curcumin and piperine with antifungals has shown synergistic effects against multiresistant clinical isolates of Candida albicans representing an alternative drug research for the treatment of clinical candidiasis. [ABSTRACT FROM AUTHOR]