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Drug and Therapeutics Bulletin May 1980
Clinical Trial
Topics: Arthrodermataceae; Clinical Trials as Topic; Dermatomycoses; Econazole; Female; Humans; Imidazoles
PubMed: 6993167
DOI: No ID Found -
Small (Weinheim An Der Bergstrasse,... Jun 2023Insufficienct T lymphocyte infiltration and unresponsiveness to immune checkpoint blockade therapy are still major difficulties for the clinical treatment of pancreatic...
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.
Topics: Humans; Econazole; Biliverdine; Immune Checkpoint Inhibitors; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Immunotherapy; Water; Tumor Microenvironment; Cell Line, Tumor
PubMed: 36899444
DOI: 10.1002/smll.202207201 -
Clinics in Dermatology Mar 2010Aspergillus and Candida spp are the most frequently isolated fungi in patients with otomycosis. The diagnosis of otitis externa relies on the patient's history,... (Review)
Review
Aspergillus and Candida spp are the most frequently isolated fungi in patients with otomycosis. The diagnosis of otitis externa relies on the patient's history, otoscopic examination under microscopic control, and imaging studies. Direct preparation of the specimens, particularly with optical brighteners, mycologic culture, and histologic examination, is very important and strongly recommended for the correct diagnosis. Patients with noninvasive fungal otitis externa should be treated with intense débridement and cleansing, and topical antifungals. Topical antifungals, such as clotrimazole, miconazole, bifonazole, ciclopiroxolamine, and tolnaftate, are potentially safe choices for the treatment of otomycosis, especially in patients with a perforated eardrum. The oral triazole drugs, itraconazole, voriconazole, and posaconazole are effective against Candida and Aspergillus, with good penetration of bone and the central nervous system. These drugs are essential in the treatment of patients with malignant fungal otitis externa complicated by mastoiditis and meningitis.
Topics: Administration, Topical; Amphotericin B; Anti-Infective Agents; Antifungal Agents; Clotrimazole; Drug Resistance, Fungal; Econazole; Humans; Itraconazole; Miconazole; Mycoses; Ointments; Otitis Externa
PubMed: 20347664
DOI: 10.1016/j.clindermatol.2009.12.003 -
Drugs Sep 1978Econazole1 is a recently introduced imidazole antifungal agent which is very closely related structurally to another imidazole derivative, miconazole. For local... (Review)
Review
Econazole1 is a recently introduced imidazole antifungal agent which is very closely related structurally to another imidazole derivative, miconazole. For local application the nitrate salt of econazole is used, while in preliminary investigations of systemic use in a few patients econazole base has been administered orally or intravenously. In uncontrolled studies in large numbers of patients, econazole nitrate has been administered topically in the treatment of dermatomycoses due to a wide variety of fungi, and vaginally in the treatment of vaginal candidosis; but it has not been compared with any other antifungal drug in controlled therapeutic trials in mycoses of the skin and has only been compared with nystatin in a few patients with vaginal candidosis. Until adequate comparative studies are done the relative place of econazole in the treatment of dermatomycoses and vaginal condidosis, compared with traditional antifungal agents and with other imidazole derivatives such as miconazole or clotrimazole, cannot be clearly stated. Nevertheless, econazole nitrate is an effective antifungal drug. In dermatological studies about 90% of a large number of patients were cured, often after a relatively short treatment period (2 to 6 weeks, as occurs with other imidazole antifungal agents). The cure rate was only slightly lower (about 85%) in patients with severe mycoses of many years' duration than in those whose infections were of more recent onset. In vaginal candidosis a 3-day treatment regimen using a 150mg suppository once daily was only slightly less effective (85% mycological cure rate) than a 15-day regimen using a 50mg dose (suppository or cream) once daily (90% cure rate). A 3 to 5 day 'higher' dose regimen was slightly more effective than a standard 15-day regimen of nystatin vaginal inserts in a small group of patients with vaginal candidosis. The convenience of the higher-dose shorter term regimen would likely be an important advantage to most patients. Whether other agents useful in vaginal candidosis would be as effective as econazole were they to be used in this way, has not been determined. Topical or intravaginal econazole nitrate has usually been well tolerated, side effects being limited to local irritation in about 1 to 4% of patients in most studies.
Topics: Adult; Animals; Bacterial Infections; Candidiasis, Vulvovaginal; Child; Dogs; Drug Resistance, Microbial; Econazole; Female; Fertility; Fetus; Haplorhini; Humans; Imidazoles; In Vitro Techniques; Lethal Dose 50; Mice; Mycoses; Otitis; Pregnancy; Rabbits; Rats; Sinusitis; Skin Absorption; Skin Diseases, Infectious
PubMed: 98315
DOI: 10.2165/00003495-197816030-00001 -
International Journal of Pharmaceutics Nov 2015Econazole is a commonly used azole antifungal in clinical treatment of superficial fungal infections. It is generally used as conventional cream and gel preparations... (Review)
Review
Econazole is a commonly used azole antifungal in clinical treatment of superficial fungal infections. It is generally used as conventional cream and gel preparations under the brand names of Spectazole (United States), Ecostatin (Canada), Pevaryl (Western Europe). Treatment efficiency of antifungal drugs depends on their penetration through target layers of skin at effective concentrations. Econazole's poor water solubility limits its bioavailability and antifungal effects. Therefore, formulation strategies have been examined for delivering econazole through targeted skin sites. The present overview focuses on novel nano-based formulation approaches used to improve econazole penetration through skin for treatment of superficial fungal infections.
Topics: Antifungal Agents; Chemistry, Pharmaceutical; Drug Carriers; Drug Stability; Econazole; Lipids; Liposomes; Micelles; Nanoparticles; Silicon Dioxide; Skin Absorption; Solubility
PubMed: 26383840
DOI: 10.1016/j.ijpharm.2015.09.015 -
The Journal of Antimicrobial... Feb 2022Bacterial antibiotic tolerance is responsible for the recalcitrance of chronic infections. This study aims to investigate a potential drug that can effectively kill...
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.
Topics: Adjuvants, Pharmaceutic; Animals; Anti-Bacterial Agents; Bacteria; Econazole; Mice; Proton-Motive Force
PubMed: 34747463
DOI: 10.1093/jac/dkab384 -
Journal of Pharmaceutical Sciences May 2018Econazole is a feasible alternative treatment in the management of fungal keratitis. Nevertheless, its low water solubility is considered the main limitation to the...
Econazole is a feasible alternative treatment in the management of fungal keratitis. Nevertheless, its low water solubility is considered the main limitation to the incorporation into ophthalmic formulations. In this work, econazole nitrate is solubilized by using cyclodextrins to achieve an optimum therapeutic concentration. Phase solubility diagrams suggest α-cyclodextrin as the most effective cyclodextrin and later the inclusion complex formed with this one was characterized in solution by 1D, 2D-NMR, and molecular modeling. Econazole-α-cyclodextrin inclusion complex was included in 2 types of ocular hydrogels: a natural polysaccharides ion-sensitive hydrogel and a hyaluronic acid hydrogel. Both of them show no ocular irritation in the hen's egg test on chorioallantoic membrane assay and a controlled econazole release over time. Permeability studies suggest that hydrogels do not modify the econazole nitrate permeability through bovine cornea in comparison with an econazole-α-cyclodextrin inclusion complex solution. Finally, ocular biopermanence studies performed using positron emission tomography show these hydrogels present a high retention time on the eye. Results suggest the developed formulations have a high potential as vehicles for the econazole topical ocular administration as fungal keratitis treatment.
Topics: Administration, Ophthalmic; Animals; Antifungal Agents; Cattle; Chickens; Cornea; Delayed-Action Preparations; Drug Compounding; Econazole; Fungi; Hydrogels; Keratitis; Solubility; alpha-Cyclodextrins
PubMed: 29305870
DOI: 10.1016/j.xphs.2017.12.028 -
Journal of Materials Science. Materials... May 2018While antibiotic-eluting polymethylmethacrylate space maintainers have shown efficacy in the treatment of bacterial periprosthetic joint infection and osteomyelitis,...
While antibiotic-eluting polymethylmethacrylate space maintainers have shown efficacy in the treatment of bacterial periprosthetic joint infection and osteomyelitis, antifungal-eluting space maintainers are associated with greater limitations for treatment of fungal musculoskeletal infections including limited elution concentration and duration. In this study, we have designed a porous econazole-eluting space maintainer capable of greater inhibition of fungal growth than traditional solid space maintainers. The eluted econazole demonstrated bioactivity in a concentration-dependent manner against the most common species responsible for fungal periprosthetic joint infection as well as staphylococci. Lastly, these porous space maintainers retain compressive mechanical properties appropriate to maintain space before definitive repair of the joint or bony defect.
Topics: Antifungal Agents; Aspergillus fumigatus; Biocompatible Materials; Candida albicans; Econazole; Materials Testing; Mycoses; Polymethyl Methacrylate; Porosity; Prosthesis-Related Infections; Staphylococcus aureus
PubMed: 29752591
DOI: 10.1007/s10856-018-6073-1 -
European Journal of Pharmaceutics and... Apr 2016In this work, we propose pharmaceutical textiles imprinted with lipid microparticles of Econazole nitrate (ECN) as a mean to improve patient compliance while maintaining...
In this work, we propose pharmaceutical textiles imprinted with lipid microparticles of Econazole nitrate (ECN) as a mean to improve patient compliance while maintaining drug activity. Lipid microparticles were prepared and characterized by laser diffraction (3.5±0.1 μm). Using an optimized screen-printing method, microparticles were deposited on textiles, as observed by scanning electron microscopy. The drug content of textiles (97±3 μg/cm(2)) was reproducible and stable up to 4 months storage at 25 °C/65% Relative Humidity. Imprinted textiles exhibited a thermosensitive behavior, as witnessed by a fusion temperature of 34.8 °C, which enabled a larger drug release at 32 °C (temperature of the skin) than at room temperature. In vitro antifungal activity of ECN textiles was compared to commercial 1% (wt/wt) ECN cream Pevaryl®. ECN textiles maintained their antifungal activity against a broad range of Candida species as well as major dermatophyte species. In vivo, ECN textiles also preserved the antifungal efficacy of ECN on cutaneous candidiasis infection in mice. Ex vivo percutaneous absorption studies demonstrated that ECN released from pharmaceutical textiles concentrated more in the upper skin layers, where the fungal infections develop, as compared to dermal absorption of Pevaryl®. Overall, these results showed that this technology is promising to develop pharmaceutical garments textiles for the treatment of superficial fungal infections.
Topics: Administration, Cutaneous; Animals; Antifungal Agents; Candida; Candidiasis; Drug Carriers; Econazole; Female; Lipids; Mice; Molecular Imprinting; Skin; Skin Absorption; Swine; Temperature; Textiles
PubMed: 26883854
DOI: 10.1016/j.ejpb.2016.02.003 -
Analytical Biochemistry Aug 2020Econazole is a widely used chiral antifungal drug. In this paper, an enantioselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed...
Econazole is a widely used chiral antifungal drug. In this paper, an enantioselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for determination of econazole enantiomers in rat plasma for the first time. After addition of the internal standard (IS) clotrimazole, plasma samples were extracted by liquid-liquid extraction with n-hexane:2-propanol (98.5:1.5, v/v). Baseline separation of the enantiomers was achieved on a Chiralpak® IC column (250 mm × 4.6 mm, 5 μm) using acetonitrile-ammonium acetate buffer (5 mM) (85:15, v/v) as mobile phase. The detection of the analytes was performed in multiple reaction monitoring (MRM) mode with positive electrospray ionization. Transitions of m/z 381.07 → 124.92 and 276.78 → 164.92 were monitored for econazole enantiomers and clotrimazole, respectively. The linear range was 0.20-50.00 ng/mL with the lower limit of quantification of 0.20 ng/mL for both econazole enantiomers in plasma. The intra-day and inter-day precisions were not exceeding 10.2% and the accuracies were within ±15.0%. The validated method was successfully applied to the stereoselective pharmacokinetic study of econazole enantiomers in rat plasma after transdermal administration of racemic econazole nitrate cream. Significant differences were observed in C, AUC and CL/F of econazole enantiomers, indicating the enantioselective pharmacokinetic behavior of econazole in rats.
Topics: Administration, Cutaneous; Animals; Econazole; Male; Molecular Structure; Rats; Rats, Wistar; Stereoisomerism; Tissue Distribution
PubMed: 32473119
DOI: 10.1016/j.ab.2020.113791