Clotrimazole

BackgroundClotrimazole is an azole derivative with promising anti-cancer effects. This drug interferes with the activity of glycolytic enzymes altering their cellular distribution and inhibiting their activities. The aim of the present study was to analyze the effects of clotrimazole on the growth pattern of breast cancer cells correlating with their metabolic profiles.Methodology/principal findingsThree cell lines derived from human breast tissue (MCF10A, MCF-7 and MDA-MB-231) that present increasingly aggressive profiles were used. Clotrimazole induces a dose-dependent decrease in glucose uptake in all three cell lines, with K(i) values of 114.3±11.7, 77.1±7.8 and 37.8±4.2 µM for MCF10A, MCF-7 and MDA-MB-231, respectively. Furthermore, the drug also decreases intracellular ATP content and inhibits the major glycolytic enzymes, hexokinase, phosphofructokinase-1 and pyruvate kinase, especially in the highly metastatic cell line, MDA-MB-231. In this last cell lineage, clotrimazole attenuates the robust migratory response, an effect that is progressively attenuated in MCF-7 and MCF10A, respectively. Moreover, clotrimazole reduces the viability of breast cancer cells, which is more pronounced on MDA-MB-231.Conclusions/significanceClotrimazole presents deleterious effects on two human breast cancer cell lines metabolism, growth and migration, where the most aggressive cell line is more affected by the drug. Moreover, clotrimazole presents little or no effect on a non-tumor human breast cell line. These results suggest, at least for these three cell lines studied, that the more aggressive the cell is the more effective clotrimazole is.

BackgroundAlthough the connection between ascending infection and preterm birth is undisputed, research focused on finding effective treatments has been disappointing. However evidence that eradication of Candida in pregnancy may reduce the risk of preterm birth is emerging. We conducted a pilot study to assess the feasibility of conducting a large randomized controlled trial to determine whether treatment of asymptomatic candidiasis in early pregnancy reduces the incidence of preterm birth.MethodsWe used a prospective, randomized, open-label, blinded-endpoint (PROBE) study design. Pregnant women presenting at ResultsOf 779 women approached, 500 (64%) participated in candidiasis screening, and 98 (19.6%) had asymptomatic vaginal candidiasis and were randomized to clotrimazole or usual care. Women were not inconvenienced by participation in the study, laboratory testing and medication dispensing were problem-free, and the follow-up rate was 99%. There was a tendency towards a reduction in spontaneous preterm birth among women with asymptomatic candidiasis who were treated with clotrimazole RR = 0.33, 95%CI 0.04-3.03.ConclusionsA large, adequately powered, randomized trial of clotrimazole to prevent preterm birth in women with asymptomatic candidiasis is both feasible and warranted.Trial registrationAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609001052224.

Global incidence of superficial fungal infections caused by dermatophytes is high and affects around 40 million people. It is the fourth most common cause of infection. Clotrimazole, a broad spectrum imidazole antifungal agent is widely used to treat fungal infections. Conventional topical formulations of clotrimazole are intended to treat infections by effective penetration of drugs into the stratum corneum. However, drawbacks such as poor dermal bioavailability, poor penetration, and variable drug levels limit the efficiency. The present study aims to load clotrimazole into ufosomes and evaluate its topical bioavailability. Clotrimazole loaded ufosomes were prepared using cholesterol and sodium oleate by thin film hydration technique and evaluated for size, polydispersity index, and entrapment efficiency to obtain optimized formulation. Optimized formulation was characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). Skin diffusion studies and tape-stripping were performed using human skin to determine the amount of clotrimazole accumulated in different layers of the skin. Results showed that the optimized formulation had vesicle size <250 nm with ~84% entrapment efficiency. XRD and DSC confirmed the entrapment of clotrimazole into ufosomes. No permeation was observed through the skin up to 24 h following the permeation studies. Tape-stripping revealed that ufosomes led to accumulation of more clotrimazole in the skin compared to marketed formulation (Perrigo). Overall, results revealed the capability of ufosomes in improving the skin bioavailability of clotrimazole.

BackgroundIntravaginal drug administration is the most promising strategy for treating vaginal infections to protect women's health, such as vulvovaginal candidiasis (VVC). However, conventional vaginal formulations in the clinic face challenges such as drug leakage and low bioavailability due to the mucus barrier and vaginal self-cleaning behavior. To address these limitations, we designed and optimized clotrimazole-loaded PLGA non-spherical microparticles (CPNMs) for vaginal drug delivery.MethodsCPNMs and clotrimazole-loaded PLGA porous microspheres (CPMs) were prepared by the double emulsion-solvent evaporation method. The physicochemical features and in vitro drug release kinetics were characterized, and the effect of shape on drug delivery were also investigated. After intravaginal administration of CPMs and CPNMs, the pharmacokinetics and biocompatibility in the vagina of mice were studied.ResultsBoth CPMs and CPNMs exhibited sustained release features in vitro. Initially, there was a rapid release within the first 24 h and the cumulative release of CPMs and CPNMs was 46.55% and 56.89% over 7 days, respectively. Compared to CPMs, CPNMs demonstrated an extended drug release in vivo, maintaining a residence duration of at least 72 h, which was beneficial for clotrimazole delivery at a high concentration in the vagina of mice. Histological evaluation demonstrated the low cytotoxicity and good biocompatibility of CPNMs, with no obvious damage to vaginal epithelial cells.ConclusionThis vaginal drug delivery system offers potential applications for managing VVC, along with other health concerns in women.