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Ketoconazole - DOAJ

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Last Updated: 11 September 2022

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An FDA-Approved Antifungal, Ketoconazole, and Its Novel Derivative Suppress tGLI1-Mediated Breast Cancer Brain Metastasis by Inhibiting the DNA-Binding Activity of Brain Metastasis-Promoting Transcription Factor tGLI1

To selectively kill tGLI1-expressing breast cancer cells and breast cancer stem cells, we screened 1527 compounds using two sets of isogenic breast cancer and brain-tropic breast cancer cell lines engineered to stably demonstrate the control, the GLI1 gene, and breast cancer stem cells, but not tGLI1-negative breast cancer cells and breast cancer stem cells. Two experimental mouse metastasis studies have shown that systemic KCZ administration delayed the preferential brain metastasis of tGLI1-positive breast cancer and reduced the development of new tGLI1-positive BCBM without liver toxicities. The KCZ-7 exhibited increased bloodu2013brain barrier penetration than KCZ/KCZ-5 and more effectively reduced BCBM frequency, which more dramatically reduced the BCBM frequency. Our report establishes the underlying causes of action for using KCZ and KCZ-7 for treating and preventing BCBM, as well as determining their mechanisms of action.

Source link: https://doi.org/10.3390/cancers14174256


Differential effects of ketoconazole, fluconazole, and itraconazole on the pharmacokinetics of pyrotinib in vitro and in vivo

In vitro, pyrotinib's pharmacokinetics, DDIs between pyrotinib and three azoles were investigated with Sprague-Dawley rat liver microsomes to better understand the effects of azole antifungal drugs on pyrotinib's pharmacokinetics, DDIs between pyrotinib and three azoles. In vitro experiments revealed that ketoconazole, fluconazole, and itraconazole's IC50 values were 0. 06, 11. 55, and 0. 27 u03bcM, respectively, indicating that these medications may reduce the clearance rate of pyrotinib at different degrees. In rat experiments, coadministration of pyrotinib with ketoconazole or fluconazole could dramatically raise the Cmax and AUC values and decrease the clearance rate of pyrotinib, particularly for ketoconazole or fluconazole. Both in vitro and in vivo, these results showed that ketoconazole and fluconazole could significantly reduce pyrotinib metabolism. In a clinic, more caution should be paid when pyrotinib is mixed with azole antifungal agents, but further investigation is still needed in the future.

Source link: https://doi.org/10.3389/fphar.2022.962731


Ucuùba ( Virola surinamensis ) Fat-Based Nanostructured Lipid Carriers for Nail Drug Delivery of Ketoconazole: Development and Optimization Using Box-Behnken Design

U00f9ba fat is a fat obtained from a plant that was discovered in South America, most in Amazonian Brazil. In the case of an application for the treatment of onychomycosis and other persistent fungal infections, Ucu00f9ba fat was used for the manufacture of ketoconazole-loaded nanostructured lipid carriers. A Box-Behnken set of experiments was used to test out the creation and optimization of Ucu-ba fat-based NLC. The independent variables were surfactant concentration, liquid lipids concentration, and solid lipids concentration, with solid lipids concentration as the target, while the outcomes of concern were particle size, polydispersity index, and drug encapsulation effectiveness. The optimized formulations were tested and showed particle size in accordance with the predicted value, i. e. , 33. 6 nm and 74. 6 nm, respectively, and the predicted value. The optimized formulations were also tested using multiple methods in order to determine the solid state of drug and excipients, particle morphology, drug release, and interactions among the formulation components.

Source link: https://doi.org/10.3390/pharmaceutics11060284


The Antifungal and Ocular Permeation of Ketoconazole from Ophthalmic Formulations Containing Trans-Ethosomes Nanoparticles

Ketoconazole, a non-oxide broad-spectrum antifungal agent that can be used to mask corneal permeation, is characterized by its poor aqueous solubility and high molecular weight. The aim was to produce an ophthalmic formulation with optimized trans-ethosomal vesicles to improve KET ocular permeation, antifungal activity, rapid drug removal, and a short elimination half-life. The optimized vesicles were spherical and had an average size of 151. 36 nm, an entrapment rate of 94. 97 u00b1 5. 4 percent, and a range of 95. 44 4. 3 percent, according to a zeta potential value of 86. 73 nm, a zeta potential of 93. 74 u00b1 8. 73 %, with a maximum yield of 94 4. 3 73 n 73 zeta u00b1 8. 73 81 u00b1 94 94. Following administration with the optimized vesicles, the antifungal activity of KET was significantly enhanced. The trans-ethosomes vesicles were able to penetrate into the posterior eye segment without any harmful effects, despite no harmful effects. According to reports, the in situ developed gel formulation laced with KET trans-ethosomes vesicles represents a promising ocular delivery system for the treatment of deep fungal eye infections.

Source link: https://doi.org/10.3390/pharmaceutics13020151

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions