Structural mechanism of TRPV5 inhibition by econazole.

The calcium-selective TRPV5 channel activated by phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is involved in calcium homeostasis. Recently, cryoelectron microscopy (cryo-EM) provided molecular details of TRPV5 modulation by exogenous and endogenous molecules. However, the details of TRPV5 inhibition by the antifungal agent econazole (ECN) remain elusive due to the low resolution of the currently available structure. In this study, we employ cryo-EM to comprehensively examine how the ECN inhibits TRPV5. By combining our structural findings with site-directed mutagenesis, calcium measurements, electrophysiology, and molecular dynamics simulations, we determined that residues F472 and L475 on the S4 helix, along with residue W495 on the S5 helix, collectively constitute the ECN-binding site. Additionally, the structure of TRPV5 in the presence of ECN and PI(4,5)P2, which does not show the bound activator, reveals a potential inhibition mechanism in which ECN competes with PI(4,5)P2, preventing the latter from binding, and ultimately pore closure.

Econazole selectively induces cell death in NF1-homozygous mutant tumor cells.

Cutaneous neurofibromas (cNFs) are tumors that develop in more than 99% of individuals with neurofibromatosis type 1 (NF1). They develop in the dermis and can number in the thousands. cNFs can be itchy and painful and negatively impact self-esteem. There is no US Food and Drug Administration (FDA)-approved drug for their treatment. Here, we screen a library of FDA-approved drugs using a cNF cell model derived from human induced pluripotent stem cells (hiPSCs) generated from an NF1 patient. We engineer an NF1 mutation in the second allele to mimic loss of heterozygosity, differentiate the NF1+/- and NF1-/- hiPSCs into Schwann cell precursors (SCPs), and use them to screen a drug library to assess for inhibition of NF1-/- but not NF1+/- cell proliferation. We identify econazole nitrate as being effective against NF1-/- hiPSC-SCPs. Econazole cream selectively induces apoptosis in Nf1-/- murine nerve root neurosphere cells and human cNF xenografts. This study supports further testing of econazole for cNF treatment.

The effect of charges on the corneal penetration of solid lipid nanoparticles loaded Econazole after topical administration in rabbits.

Fungal keratitis is an infectious disease caused by pathogenic fungi with a high blindness rate. Econazole (ECZ) is an imidazole antifungal drug with insoluble ability. Econazole-loaded solid lipid nanoparticles (E-SLNs) were prepared by microemulsion method, then modified with positive and negative charge. The mean diameter of cationic E-SLNs, nearly neutral E-SLNs and anionic E-SLNs were 18.73±0.14, 19.05±0.28, 18.54±0.10 nm respectively. The Zeta potential of these different charged SLNs formulations were 19.13±0.89, -2.20±0.10, -27.40±0.67 mV respectively. The Polydispersity Index (PDI) of these three kinds of nanoparticles were all about 0.2. The Transmission Electron Microscopy (TEM) and Differential Scanning Calorimetry (DSC) analysis showed that the nanoparticles were a homogeneous system. Compared with Econazole suspension (E-Susp), SLNs exhibited sustained release capability, stronger corneal penetration and enhanced inhibition of pathogenic fungi without irritation. The antifungal ability was further improved after cationic charge modification compared with E-SLNs. Studies on pharmacokinetics showed that the order of the AUC and t1/2 of different preparations was cationic E-SLNs > nearly neutral E-SLNs > anionic E-SLNs > E-Susp in cornea and aqueous humor. It was shown that SLNs could increase corneal penetrability and ocular bioavailability while these capabilities were further enhanced with positive charge modification compared with negative charge ones.

Nano-Econazole Enhanced PD-L1 Checkpoint Blockade for Synergistic Antitumor Immunotherapy against Pancreatic Ductal Adenocarcinoma.

Insufficienct T lymphocyte infiltration and unresponsiveness to immune checkpoint blockade therapy are still major difficulties for the clinical treatment of pancreatic ductal adenocarcinoma (PDAC). Although econazole has shown promise in inhibiting PDAC growth, its poor bioavailability and water solubility limit its potential as a clinical therapy for PDAC. Furthermore, the synergistic role of econazole and biliverdin in immune checkpoint blockade therapy in PDAC remains elusive and challenging. Herein, a chemo-phototherapy nanoplatform is designed by which econazole and biliverdin can be co-assembled (defined as FBE NPs), which significantly improve the poor water solubility of econazole and enhance the efficacy of PD-L1 checkpoint blockade therapy against PDAC. Mechanistically, econazole and biliverdin are directly released into the acidic cancer microenvironment, to activate immunogenic cell death via biliverdin-induced PTT/PDT and boost the immunotherapeutic response of PD-L1 blockade. In addition, econazole simultaneously enhances PD-L1 expression to sensitize anti-PD-L1 therapy, leading to suppression of distant tumors, long-term immune memory effects, improved dendritic cell maturation, and tumor infiltration of CD8+ T lymphocytes. The combined FBE NPs and α-PDL1 show synergistic antitumor efficacy. Collectively, FBE NPs show excellent biosafety and antitumor efficacy by combining chemo-phototherapy with PD-L1 blockade, which has promising potential in a precision medicine approach as a PDAC treatment strategy.

A Novel Approach To Identify Inhibitors of Iron Acquisition Systems of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen that has been declared by the World Health Organization as a "priority 1 critical pathogen" needing immediate new strategies for chemotherapy. During infection, P. aeruginosa uses redundant mechanisms to acquire ferric, heme (Hm), or ferrous iron from the host to survive and colonize. Significant efforts have been undertaken to develop siderophore blockers to inhibit ferric iron acquisition by P. aeruginosa, but there is a lack of inhibitors that can block Hm or ferrous iron acquisition by P. aeruginosa. We developed and employed a targeted high-throughput screen (HTS) and identified a molecule(s) that can specifically inhibit the Hm and ferrous iron acquisition systems of P. aeruginosa. Our targeted approach relies on screening a small-molecule library against P. aeruginosa under three growth conditions, where the only variable was the iron source (ferric, Hm, or ferrous iron). Each condition served as a counterscreen for the other, and we identified molecules that inhibit the growth of P. aeruginosa in the presence of only Hm or ferrous iron. Our data indicate that econazole, bithionate, and raloxifene inhibit the growth of P. aeruginosa in the presence of Hm and that oxyquinoline inhibits the growth of P. aeruginosa in the presence of ferrous iron. These iron-specific inhibitors do not interfere with the activity of meropenem, a commercial antipseudomonal, and can also increase meropenem activity. In conclusion, we present a proof of concept of a successful targeted conditional screening method by which we can identify specific iron acquisition inhibitors. This approach is highly adaptable and can easily be extended to any other pathogen. IMPORTANCE Since acquiring iron is paramount to P. aeruginosa's survival and colonization in the human host, developing novel strategies to block the access of P. aeruginosa to host iron will allow us to starve it of an essential nutrient. P. aeruginosa uses siderophore, heme, or ferrous iron uptake systems to acquire iron in the human host. We have developed a novel approach through which we can directly identify molecules that can prevent P. aeruginosa from utilizing heme or ferrous iron. This approach overcomes the need for the in silico design of molecules and identifies structurally diverse biologically active inhibitor molecules. This screening approach is adaptable and can be extended to any pathogen. Since Gram-negative pathogens share many similarities in iron acquisition at both the mechanistic and molecular levels, our screening approach presents a significant opportunity to develop novel broad-spectrum iron acquisition inhibitors of Gram-negative pathogens.

The structure and characterization of human cytochrome P450 8B1 supports future drug design for nonalcoholic fatty liver disease and diabetes.

Human cytochrome P450 8B1 (CYP8B1) is involved in conversion of cholesterol to bile acids. It hydroxylates the steroid ring at C12 to ultimately produce the bile acid cholic acid. Studies implicated this enzyme as a good drug target for nonalcoholic fatty liver disease and type 2 diabetes, but there are no selective inhibitors known for this enzyme and no structures to guide inhibitor development. Herein, the human CYP8B1 protein was generated and used to identify and characterize interactions with a series of azole inhibitors, which tend to be poorly selective P450 inhibitors. Structurally related miconazole, econazole, and tioconazole bound with submicromolar dissociation constants and were effective inhibitors of the native reaction. CYP8B was cocrystallized with S-tioconazole to yield the first X-ray structure. This inhibitor bound in the active site with its azole nitrogen coordinating the heme iron, consistent with inhibitor binding and inhibition assay data. Additionally, the CYP8B1 active site was compared with similar P450 enzymes to identify features that may facilitate the design of more selective inhibitors. Selective inhibitors should promote a better understanding of the role of CYP8B1 inhibition in normal physiology and disease states and provide a possible treatment for nonalcoholic fatty liver disease and type 2 diabetes.

Diversity of Parengyodontium spp. strains isolated from the cultural heritage environment: Phylogenetic diversity, phenotypical diversity, and occurrence.

Parengyodontium album is a fungal species that frequently occurs in the cultural heritage environment. Although three subclades were initially described in the species, no study has sought to determine the occurrence of each subclade in the cultural heritage context. These subclades are easily distinguishable phylogenetically, but their morphological identification is more difficult. Eighteen strains isolated from different cultural sites and initially identified as P. album were studied phylogenetically, morphologically, and in terms of their susceptibility to econazole nitrate 0.2%, an antifungal product used as preservation treatment in cultural heritage domain. The phylogenetic study revealed that all studied strains belonged to P. album subclade 1 or P. torokii (P. album subclade 3) and none belonged to P. album subclade 2. The morphological study revealed the best characteristics to differentiate the three subclades/species, namely, the ability of the strains to grow at 32 C and 35 C on potato dextrose agar (PDA) medium and the shape of conidia. Finally, the strains displayed variable susceptibilities to econazole nitrate, with no apparent link to any particular subclade/species.

In vitro activity of 23 antifungal drugs against 54 clinical and environmental Aspergillus oryzae isolates.

The treatment of invasive aspergillosis caused by cryptic species remains a challenge due to the lack of randomised clinical trials and investigation of the efficacy and safety of different therapeutic strategies. We aimed to evaluate the in vitro activity of 23 conventional and new antifungal drugs against 54 clinical and environmental Aspergillus oryzae isolates by using the Clinical and Laboratory Standards Institute (CLSI) standard M38-A3. The lowest geometric mean MIC values were found for luliconazole and lanoconazole (0.001 µg/ml), followed by anidulafungin (0.104 µg/ml), posaconazole (0.15 µg/ml), itraconazole (0.37 µg/ml), efinaconazole (0.5 µg/ml), voriconazole (0.51 µg/ml), tavaborole (0.72 µg/ml), and amphotericin B (0.79 µg/ml). In contrast, ketoconazole, terbinafine, econazole, tioconazole, ravuconazole, miconazole, nystatin, clotrimazole, griseofulvin, sertaconazole, natamycin, tolnaftate, and fluconazole had no or low activity. Further studies are required to determine how well this in vitro activity translates into in vivo efficacy.

Synergistic Antimicrobial Effect of Colistin in Combination with Econazole against Multidrug-Resistant Acinetobacter baumannii and Its Persisters.

Colistin is a last-line antibiotic which acts by causing membrane permeabilization in Gram-negative bacteria. However, its clinical value has been limited by its toxicity and the emergence of resistant organisms. In this study, we showed that econazole and colistin can act synergistically to produce a strong antimicrobial effect sufficient for eradication of starvation-induced tolerant and multidrug-resistant populations of Acinetobacter baumannii, a notorious pathogen causing recalcitrant infections, both in vitro and in mouse infection models. Investigation of the underlying mechanism showed that, while colistin disrupts the membrane structure, econazole causes the dissipation of proton motive force, eliciting a vicious cycle of membrane structural damages and disruption of membrane protein functions, and eventually cell death. This drug combination therefore achieves our goal of using a much smaller dosage of colistin to produce a much stronger antimicrobial effect to tackle the problems of toxicity and resistance associated with colistin usage. IMPORTANCE Findings described in this study constitute concrete evidence that it is possible to significantly enhance the antimicrobial activity of colistin by using an antifungal drug, econazole, as a colistin adjuvant. We showed that this drug combination can kill not only multidrug-resistant A. baumannii but also the tolerant subpopulation of such strains known as persisters, which may cause chronic and recurrent infections in clinical settings. The synergistic killing effect of the econazole and colistin combination was also observable in mouse infection models at a very low concentration, suggesting that such a drug combination has high potential to be used clinically. Findings in this study therefore have important implications for enhancing its clinical application potential as well as developing new approaches to enhance treatment effectiveness and reduce suffering in patients.

Single ascending dose safety, tolerability, and pharmacokinetic study of econazole in healthy volunteers.

INTRODUCTION: Econazole has been found efficacious as antitubercular in in vitro and in vivo animal studies. However, limited information is available for its safety and pharmacokinetics in humans. In our present study we have conducted single ascending dose, safety, and pharmacokinetic evaluation in healthy human volunteers with the purpose of enabling translation for tuberculosis. METHODS: This study was conducted as a single-center, ascending-dose, placebo-controlled, double blind design. Three ascending dose were chosen (250 , 500 , and 1000 mg) to be administered as a single oral dose. The volunteers were screened for potential eligibility. Participants were randomized to receive either Econazole or Placebo in a 6:2 design. Safety assessments and pharmacokinetic evaluations were carried out for each cohort. RESULTS: Econazole was found to be safe at all dose levels. No serious or severe adverse events occurred during the study. The AUC (0-∞) showed a response relationship with a value of 49 ± 3.47 h* µg/ml, 17. 86 ± 8.40 hr* µg/ml, 35.54 ± 13.94 hr* µg/ml for 250 mg, 500 mg, and 1000 mg, respectively. CONCLUSION: Based on the findings of our study, a dose of 500 mg Econazole, once a day orally was considered as appropriate for further evaluation.

Econazole as adjuvant to conventional antibiotics is able to eradicate starvation-induced tolerant bacteria by causing proton motive force dissipation.

OBJECTIVES: Bacterial antibiotic tolerance is responsible for the recalcitrance of chronic infections. This study aims to investigate a potential drug that can effectively kill antibiotic-tolerant bacteria and evaluate the ability of this drug on the eradication of tolerant cells both in vitro and in vivo. METHODS: The in vitro effect of econazole on eradicating starvation-induced tolerant bacterial populations was studied by testing the amount of survival bacteria in the presence of econazole combining conventional antibiotics. Proton motive force (PMF) was determined after econazole treatment by DiOC2(3). Finally, mouse infection models were used to detect the ability of econazole on killing the tolerant populations in vivo. RESULTS: Econazole eradicated starvation-induced tolerant cells of various bacterial species within 24 or 96 h when used in combination with conventional antibiotics. Moreover, mouse survival rate drastically increased along with the decrease of in vivo bacterial count after treatment of infected mice with the econazole and ceftazidime combination for 72 h. PMF was found to have dissipated almost completely in econazole-treated cells. CONCLUSIONS: Econazole could act in combination with conventional antibiotics to effectively eradicate bacterial tolerant cells. The combined use of econazole and ceftazidime was shown to be effective for eradicating tolerant cells in a mouse infection model. The ability of econazole to eradicate tolerant cells was due to its ability to cause dissipation of bacterial transmembrane PMF. Econazole-mediated PMF disruption is a feasible strategy for the treatment of chronic and recurrent bacterial infections.

Corrigendum to: Oleic Acid Vesicles as a New Approach for Transdermal Delivery of Econazole Nitrate: Development, Characterization, and In-vivo Evaluation in Wistar Rats.

The authors wish to add words "Research Scholar" and "Research Supervisor" to their affiliations [1]. The original article can be found online at https://doi.org/10.2174/1574891X15999201110212725 The corrected affiliation is: 1Department of Pharmaceutics, Rayat-Bahra College of Pharmacy, Hoshiarpur, Punjab 146001, India; 2Faculty of Pharma-ceutical Sciences, Department of Pharmaceutics, PCTE Group of Institutes, Ludhiana, Punjab 142021, India; 3Research Scholar, I.K. Gujral Punjab Technical University, Jalandhar-Punjab 144601, India; 4Research Supervisor, I.K. Gujral Punjab Technical University, Jalandhar-Punjab 144601, India.

Structural mechanisms of TRPV6 inhibition by ruthenium red and econazole.

TRPV6 is a calcium-selective ion channel implicated in epithelial Ca2+ uptake. TRPV6 inhibitors are needed for the treatment of a broad range of diseases associated with disturbed calcium homeostasis, including cancers. Here we combine cryo-EM, calcium imaging, and mutagenesis to explore molecular bases of human TRPV6 inhibition by the antifungal drug econazole and the universal ion channel blocker ruthenium red (RR). Econazole binds to an allosteric site at the channel's periphery, where it replaces a lipid. In contrast, RR inhibits TRPV6 by binding in the middle of the ion channel's selectivity filter and plugging its pore like a bottle cork. Despite different binding site locations, both inhibitors induce similar conformational changes in the channel resulting in closure of the gate formed by S6 helices bundle crossing. The uncovered molecular mechanisms of TRPV6 inhibition can guide the design of a new generation of clinically useful inhibitors.

Efficacy of Clotrimazole 1% Solution Compared to Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% Cream in Patient with Otomycosis.

Fungal infection of the ear canal is called Otomycosis. It is more common in hot and humid condition. There are many modalities of treatment or therapeutic agent for treatment of otomycosis. Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream is a topical antifungal agent described to be effective in the treatment of otomycosis. This study was performed to compare the efficacy of topical application clotrimazole 1% solution and Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream in the treatment of otomycosis. A controlled, randomized and open clinical trial was carried out in ENT department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2020 to July 2020. Patients diagnosed with fungal otitis externa who were treated with topical antifungals were included in this study. They were randomized into two treatment groups: i) Clotrimazole 1% solution, 2) Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream. Patients were microscopically evaluated at two weeks of treatment to determine resolution of disease. Recurrence and complications were recorded. Demographic and clinical variables were collected and analyzed, follow up and final outcomes (absence of infection) were compared between two groups. One hundred & two (102) patients were included, 51 in the clotrimazole 1% solution group and 51 in the Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream group. Predominant symptoms are pain, pruritus, aural fullness and hearing loss. Aspergillus organism was isolated most frequently (63.73%). Treatment with clotrimazole 1% solution groups resulted in 88.23% resolution vs. 80.39% resolution with Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream at 2 weeks of treatment. Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream group demonstrated higher treatment failure 11.76 and 19.60 respectively. Clotrimazole 1% solution is more effective than Econazole Nitrate 1% + Triamcinolone Acetonide 0.1% cream for uncomplicated otomycosis. More study is needed to corroborate our results.

Formulation Development, In Vitro and In Vivo Evaluation of Topical Hydrogel Formulation of Econazole Nitrate-Loaded ß-Cyclodextrin Nanosponges.

Econazole nitrate, an antifungal drug used in the handling of skin ailments, is commercially not efficient as these ailments typically require a more elevated concentration of the drug to offer an effective pharmacological retort. Like so, it is proposed to assess the effectiveness of the topical hydrogel of econazole-loaded nanosponge in the management of skin ailment(s). Econazole nitrate-laden ß-cyclodextrin nanosponges were developed by employing the melt method using ß-cyclodextrin as the organic polymer and N,N-carbonyldiimidazole as the crosslinker. The critical factors disturbing the quality of the formulation were uniquely identified by the Ishikawa diagram, and they were optimized by the statistical experiment design concept. ß-cyclodextrin loaded nanosponges were uniquely designed using the Placket-Burman approach and optimized utilizing the Box-Behnken method. The optimized nanosponges (EN-CDN) were  421.37 ± 6.19 nm in size with an entrapment efficiency of 70.13% ± 5.73%. The topical hydrogel of nanosponges (EN-TG) was prepared using carbopol 934 and pyrrolidone as permeation enhancers. In vitro skin permeation studies affirmed the improved transport crosswise the goatskin for topical hydrogel in comparison to the marketed product. EN-TG was able to control the fungal infection in the selected animal model in comparison to the marketed preparation. Stability studies reported favorably that nanogel remained stable under normal and accelerated settings.

Sertaconazole induced toxicity in HeLa cells through mitotic arrest and inhibition of microtubule assembly.

Econazole, miconazole, and sertaconazole, the structurally related azoles with imidazole moiety, were evaluated for their cytotoxicity and their ability to bind to mammalian tubulin. Our results indicated that sertaconazole and econazole bound to goat brain tubulin with a dissociation constant of 9 and 19 µM respectively, while miconazole did not bind to goat brain tubulin. Econazole, miconazole, and sertaconazole inhibited the proliferation of HeLa cells with an IC50 of 28, 98, and 38 µM respectively with sertaconazole alone inducing a mitotic block in the treated cells. Since sertaconazole bound to goat brain tubulin with higher affinity and blocked the cells at mitosis, we hypothesized that its cytotoxic mechanism might involve inhibition of tubulin and econazole which did not block the cells at mitosis may have additional targets than tubulin. Sertaconazole inhibited the polymerization of tubulin in HeLa cells and the in vitro assembled goat brain tubulin. Competitive tubulin-binding assay using colchicine and computational simulation studies showed that sertaconazole bound closer to the colchicine site and induced the tubulin dimer to adopt a "bent" conformation which is incompetent for the polymerization. Results from RT-PCR analysis of the A549 cells treated with sertaconazole indicated activation of apoptosis. Sertaconazole significantly inhibited the migration of HeLa cells and showed synergistic antiproliferative potential with vinblastine. Collectively, the results suggest that sertaconazole which is already in clinical practice could be useful as a topical chemotherapy agent for the treatment of skin cancers in combination with other systemic anticancer agents.

A Comparison of Triamcinolone Acetonide Econazole Cream and Nystatin Suspension in Treatment of Otomycosis.

OBJECTIVES/HYPOTHESIS: To compare the efficacy and adverse effects of triamcinolone acetonide econazole cream and nystatin suspension in the treatment of otomycosis, and to determine the clinical features, predisposing factors, and etiology of otomycosis. STUDY DESIGN: A prospective study. METHODS: A prospective clinical trial was conducted on 786 patients diagnosed with otomycosis. The study population was randomly divided into two treatment groups of triamcinolone acetonide econazole cream (TAEC) and nystatin suspension in a 1:1 ratio. After clearing all fungal deposits in the external auditory canal, the antimycotic drugs were locally applied for at least 2 weeks. The efficacy and adverse effects were compared between the two antifungal reagents by statistical analysis. Meanwhile, patient clinical data were collected to find out the clinical features, predisposing factors, and etiology. RESULTS: Pruritis was the most common symptom and Aspergillus niger was the leading fungal pathogen. There was high association (44.5%) of otomycosis with a history of unclean ear picking. The cure rate was 97.6% in the TAEC group and 73.5% in the nystatin group (P < .01). Treatment with TAEC resulted in 2.4% of patients complaining of discomforts (irritant dermatitis, otalgia, or headache) versus 59.8% of patients complaining discomforts treated with nystatin (P < .01). The residue rate of antifungals was 1.9% in the TAEC group and 89.9% in the nystatin group (P < .01) at the end of treatment. CONCLUSIONS: Thoroughly cleaning of the external auditory canal followed by local use of TAEC under endotoscope is an effective, convenient, and well-tolerated treatment for otomycosis. LEVEL OF EVIDENCE: 1 Laryngoscope, 131:E1640-E1646, 2021.

Development and in vitro evaluation of mucoadhesive gelatin films for the vaginal delivery of econazole.

Several strategies have been explored to obtain effective econazole nitrate (ECN) concentrations at the site of application for a prolonged time. In this paper, different gelatin-based film formulations for vaginal application were investigated, containing ECN (10% w/w with respect to gelatin) as pure drug or as drug-solid dispersions (SD). For the production of SD, different polymers were evaluated: polyvinylpyrrolidone (PVP), Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) and Gelucire® 50/13 (mixture of mono-, di- and triglycerides of fatty acids, esters of PEG 1500 and free PEG). Gelucire®-SD showed the best solubility enhancement, increasing 9.2 times the ECN solubility in pH 4.5 solution respect to pure drug; DSC and XRD analysis confirmed the crystalline form of the drug. XRD results evidenced that all gelatin-based films, containing either the drug or the SD, underwent the topotactic transformation of ECN into crystalline econazole (EC), owing to a strong interaction between the drug and the gelatin. Films containing Gelucire®-based SD displayed lower brittleness and rigidity with respect to the other samples; moreover they demonstrated good structural integrity after 24 h of incubation in the acidic solution (swelling degree of about 350%). Then, Gelucire®-SD based films were compared with the corresponding formulations cross-linked by genipin (2% w/w). The addition of genipin did not interfere with the drug-gelatin interaction. Gelucire®-SD based films showed similar release profiles to neat gelatin films, enhancing the drug release in the first 5 h and controlling the EC release over time, avoiding the use of a crosslinking additive. Finally, gelatin films containing Gelucire® solid dispersion displayed good adhesiveness and anti-Candida activity. Overall, results support the potential use of this film formulation as noncytotoxic EC delivery system for the treatment of vaginal candidiasis.

Case Report: Extensive Tinea Corporis and Inflammatory Tinea Capitis Caused by the Anthropophilic Dermatophyte Trichophyton tonsurans.

Trichophyton tonsurans is an anthropophilic dermatophyte with a worldwide distribution and is responsible for superficial mycosis with a wide range of clinical manifestations. We report two atypical cases of tinea due to T. tonsurans in two children: a case of extensive tinea corporis and a case of inflammatory tinea capitis.

Enantiomeric determination of econazole and sulconazole by electrokinetic chromatography using hydroxypropyl-ß-cyclodextrin combined with ionic liquids based on L-lysine and L-glutamic acid.

Two analytical methodologies based on the combined use of hydroxypropyl-ß-cyclodextrin and two different amino acid-based chiral ionic liquids (tetrabutylammonium-L-lysine or tetrabutylammonium-L-glutamic acid) in electrokinetic chromatography were developed in this work to perform the enantioselective determination of econazole and sulconazole in pharmaceutical formulations. The influence of different experimental variables such as buffer concentration, applied voltage, nature and concentration of the ionic liquid, temperature and injection time, on the enantiomeric separation was investigated. The combination of hydroxypropyl-ß-cyclodextrin and tetrabutylammonium-L-lysine under the optimized conditions enabled to achieve the enantiomeric determination of both drugs with high enantiomeric resolution (3.5 for econazole and 2.4 for sulconazole). The analytical characteristics of the developed methodologies were evaluated in terms of linearity, precision, LOD, LOQ and recovery showing good performance for the determination of both drugs which were successfully quantitated in pharmaceutical formulations. This work reports the first analytical methodology enabling the enantiomeric determination of sulconazole in pharmaceutical formulations.