diflucortolone + isoconazole (Travocort)

Allergic Contact Dermatitis With Erythema Multiforme-Like Features Induced by Isoconazole Nitrate.

Sbarra Giorgia G, Demichele Giuseppe G, Ambrogio Francesca F, Meduri Alexandre Raphael AR et al.

Diversity and Antifungal Susceptibility of Malassezia spp. Isolated From Brazilian Patients With Pityriasis Versicolor and Seborrheic Dermatitis.

de Pádua Oliveira Diogo Coelho DC, Possa Ana Paula AP, de Oliveira Santos Ana Raquel AR, Borges Ana Kleiber P AKP et al.

Malassezia spp. are part of the microbiota of many animals, including humans. However, under certain conditions, they can become pathogenic. Diseases associated with Malassezia include pityriasis versicolor (PV), seborrheic dermatitis (SD), Malassezia folliculitis, atopic dermatitis, psoriasis and fungemia. The present study aimed to describe the distribution of Malassezia species among Brazilian patients with PV and SD and to evaluate their susceptibility profiles to common antifungals. In this study, 102 clinical samples from patients with PV or SD were analysed. Clinical isolates of Malassezia were identified at the species level by sequencing the D1/D2 variable domains of the large subunit rRNA gene. Antifungal susceptibility was assessed using a modified microbroth dilution method adapted for the growth of Malassezia species. Among the 40 cultures obtained, six Malassezia species were identified. M. furfur was the most prevalent species (40.0%), followed by M. sympodialis (27.5%), M. globosa (15.0%), M. japonica (7.5%) and both M. yamatoensis and M. slooffiae (5.0% each). All isolates exhibited high MICs to caspofungin (> s16 μg/mL) and to isoconazole (MIC₅₀ = 8 μg/mL). Miconazole and clotrimazole showed MIC₅₀ values of 4 μg/mL, while itraconazole and ketoconazole were more active, with an MIC₅₀ of 0.125 μg/mL. This study showed the diversity of Malassezia species causing PV and SD in Brazil, including the rare species M. yamatoensis and M. japonica. These findings highlight the importance of antifungal susceptibility testing for these species to guide appropriate therapy.

Investigating the Telomerase Downregulatory Potential of Steroidal Drugs Following Pharmacophore-Based Rational; Computational and In Vitro Assessments.

Al-Karmalawy Ahmed A AA, Alabdali Aya Yaseen Mahmood AYM, Yousef Tarek A TA, Elmaaty Ayman Abo AA et al.

Inhibiting telomerase could lead to telomere shortening, chromosomal instability, and eventually cell death in cancer cells. The use of steroids in cancer treatment is significant; besides, drug repurposing can be a quicker and less expensive method of drug discovery than de novo drug development. Accordingly, diverse 280 steroidal drugs-following a pharmacophore-based rationale-were docked against telomerase receptor and compared to the co-crystallized inhibitor (BIBR1532) as a reference standard. Additionally, a molecular dynamics simulation for 200 ns was performed to confirm the docking results. Moreover, the six steroidal drugs (Betamethasone disproportionate, Beclomethasone disproportionate, Clobetasone butyrate, Desonide, diflucortolone valerate, and Hydrocortisone butyrate) were selected for further in vitro investigation. The antitumor activities of the six steroidal drugs against H1299, HuH7, HCT116, A549, MDA-MB-231, MCF7, PC3, MG63, and A375 cancer cell lines, besides OEC and HSF normal cell lines, were evaluated and compared to doxorubicin (Dox) as a reference positive standard. Especially, Clobetasone butyrate represented the better cytotoxicity against seven cancer cell lines (H1299, HuH7, HCT116, MDA-MB-231, PC3, MG63, and A375) with IC50 values of 12.56, 13.95, 12.00, 17.51, 11.69, 20.64, and 20.21 µg/mL, respectively. The outstanding antitumor six steroidal drugs were further investigated for their telomerase downregulatory potentials. All analogs recorded outstanding downregulatory results against telomerase, especially Clobetasone butyrate, Desonide, Diflucortolone valerate, and Hydrocortisone butyrate, where the protein expression for telomerase was downregulated up to 0.66-, 0.76-, 0.56-, and 0.73-fold change for clobetasone butyrate, desonide, diflucortolone valerate, and hydrocortisone butyrate, respectively, compared to the control.

Dermal Formulation Incorporating Isoconazole Nitrate Nanoparticles Offers High Absorption into Skin and Antimicrobial Effect Against Candida albicans.

Harada Ayako A, Tanaka Rie R, Otake Hiroko H, Yoshimura Masanori M et al.

Background: Isoconazole nitrate (ISN), an antifungal agent that inhibits ergosterol synthesis by blocking lanosterol 14α-demethylation, is widely used to treat candidiasis, and improving its skin retention and permeability can enhance its therapeutic efficacy. Therefore, we developed an ISN nanoparticle (ISN-NP) gel by wet-bead milling in the presence of methylcellulose (MC). Methods: These ISN nanoparticles were incorporated into a carboxypolymethylene hydrogel (Carbopol). The ISN concentration was measured using HPLC, and Wistar rats and Candida albicans were used to evaluate skin absorption and antifungal activity, respectively. Results: The ISN-NP gel exhibited a particle size distribution ranging from 60 to 220 nm, with the nanoparticles remaining stable. In addition, the ISN-NP gel demonstrated superior antifungal activity against Candida albicans. The Carbopol gel maintained appropriate viscosity and physical stability, and the ISN nanoparticles were released from the gel. Compared with microparticle-based gels (ISN-MP gels), the ISN-NP gel showed significantly enhanced drug release and transdermal permeation, with 1.54- and 1.7-fold increases, respectively. Conclusions: These findings indicate that incorporating ISN nanoparticles (nanocrystalline ISN) into a Carbopol-based gel matrix provides a promising strategy to enhance the topical delivery of this poorly water-soluble antifungal drug. Overall, this nanogel system represents a valuable platform for transdermal delivery in clinical applications.