Search Results (6)

Isoconazole nitrate (ISN) is a broad-spectrum antifungal agent whose therapeutic potential is limited by poor aqueous solubility and low bioavailability. This study aimed to enhance the solubility and physicochemical properties of ISN through the formation of inclusion complexes with methyl-β-cyclodextrin (M-β-CD) using freeze-drying (FD) and spray-drying (SD) methods. The prepared inclusion complexes were comprehensively characterized by high-performance liquid chromatography (HPLC), phase solubility analysis, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and proton nuclear magnetic resonance (¹H-NMR). Phase solubility studies revealed an AL-type solubility diagram with a 1:1 molar ratio and an apparent stability constant (K_S) of 2711 M⁻¹. Structural and thermal analyses confirmed successful inclusion complex formation and reduced crystallinity. The solubility assessment showed that ISN/M-β-CD complexes prepared by SD exhibited an approximately seven-fold higher aqueous solubility than ISN and performed better than those prepared by FD. Moreover, SD complexes demonstrated a higher drug content. These findings highlight the potential of M-β-CD-based inclusion complexation, particularly via spray-drying, as an effective strategy to enhance the solubility and bioavailability of poorly water-soluble drugs, such as ISN. Full article

Tinea nigra (TN) is a superficial fungal infection caused by the melanized fungus Hortaea werneckii, characterized by irregular dark patches, typically on the palms. This systematic review aims to evaluate the epidemiology, demographic characteristics, lesion distribution, diagnostic approaches, causative agents, and treatment outcomes of TN. The PubMed and MEDLINE databases were systematically searched using relevant keywords from January 1990 to January 2025, yielding a total of 102 cases across 42 studies. TN is more prevalent in tropical regions, with a higher incidence in the Americas (64 cases), particularly Mexico (23 cases), Brazil (17 cases), and Cuba (8 cases). The infection is more commonly observed in females (58 cases) than males (44 cases), with a mean patient age of 16.7 years (SD ± 13.58). The most frequently affected anatomical site is the palm, with 41 cases on the left palm, 34 on the right, and 5 involving both palms. Other affected sites include the soles and interdigital areas. Diagnosis typically involves direct microscopic examination using potassium hydroxide (KOH) preparation, which was performed in all cases, while cultures were conducted in 96 cases and dermoscopy was used in 14 cases. Hortaea werneckii was the predominant species isolated (74 cases), followed by Exophiala werneckii (14 cases), Pullularia werneckii (4 cases), and Aureobasidium melanogenum (3 cases). Recently, a new etiologic agent, Cyphellophora ludoviensis, was reported, among others. Over 25 treatment modalities were reported, with topical therapies being the most common. Whitfield’s ointment was used in 12 cases, followed by ketoconazole 2% cream (11 cases), and terbinafine 1% cream and isoconazole 1% cream (10 cases each). Spontaneous resolution occurred in two cases. The average treatment duration across all modalities was 4 weeks, with a 100% resolution rate. This systematic review emphasizes the importance of understanding TN’s clinical presentation, diagnostic techniques, and therapeutic strategies to optimize patient care and guide future research on this relatively uncommon fungal infection. Full article

Many antifungal agents, including isoconazole nitrate (ISN), suffer from low aqueous solubility and inconsistent dissolution kinetics, which limit their therapeutic potential. To address these challenges, this study aimed to enhance the solubility and stability of ISN through the development of inclusion complexes with hydroxypropyl-β-cyclodextrin (HP-β-CD). HP-β-CD inclusion complexes were prepared using a spray-drying technique and characterized through phase-solubility studies, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H-NMR), and differential scanning calorimetry (DSC). The inclusion complex significantly improved ISN solubility, increasing from 0.5088 mg/mL to 3.6550 mg/mL. These complexes were incorporated into a thermosensitive, mucoadhesive in situ gel system using Pluronic^® F127 and hydroxypropyl methylcellulose (HPMC) to optimize vaginal drug delivery. The formulations were evaluated for gelation temperature, viscosity, swelling behavior, and pH, confirming their suitability for vaginal application. Antimicrobial studies demonstrated that the ISN/HP-β-CD gels exhibited superior activity against Candida albicans, C. glabrata, and C. krusei compared to ISN alone. In vitro release studies further revealed sustained drug release following Peppas-Sahlin kinetics, supporting enhanced bioavailability and prolonged therapeutic action. This study demonstrates that the ISN/HP-β-CD-loaded in situ gel system offers a promising and effective approach for improving the solubility, stability, and antifungal efficacy of ISN for the treatment of vaginal infections. Full article

Background/Objectives: Excessive or inadequate use of antimicrobial drugs may lead to the emergence of resistant strains. For this reason, it is important to monitor consumption indicators to assess drugs’ utilization over time. This study aimed to analyze the consumption of medically prescribed azole antifungal drugs in mainland Portugal from 2014 to 2023, focusing on those directed to genital infections: fluconazole, isoconazole, itraconazole, and sertaconazole. Methods: For each drug, the evaluated parameters were the total number of packages, number of packages per 1000 inhabitants, defined daily dose (DDD) per 1000 inhabitants per day, and total costs. For this purpose, we used data from community pharmacies’ sales, which are available through INFARMED (the Portuguese national authority on medicines and health products). Results: Several trends emerged from data analysis. The COVID-19 pandemic negatively affected the consumption of all azole antifungal drugs included in this study. However, after 2020, fluconazole and sertaconazole consumption has been increasing. In the specific case of fluconazole, there was an increase in expenditure, although the total number of packages suffered a decrease over the 10-year study period. Additionally, the defined daily dose (DDD) per 1000 inhabitants per day for fluconazole and itraconazole was lower compared to estimates from the last available survey (2009). Conclusions: Although our findings represent a lesser pressure on fungi, further monitoring is needed to better understand the evolution of fluconazole and itraconazole consumption over time, particularly due to the trends observed in this study. Full article

The paper compares the experimental FT-IR, UV-vis, and ¹H NMR spectra of isoconazole and bifonazole with the density functional theory (DFT) calculations using different functionals. The results were compared with previously reported data related to their analogue, posaconazole. The analysis of calculated IR spectra with use of CAM-B3LYP (isoconazole) or B3LYP (bifonazole) functionals shows good accordance with the experimental IR spectrum. The best compatibility between the experimental and theoretical UV spectra was observed with the use of B3LYP or wB97XD functionals for isoconazole or bifonazole, respectively. The reason for the difference in the UV-vis spectra of isoconazole and bifonazole was discussed based on linear response time-dependent DFT and natural bond orbital methods. The calculated ¹H NMR spectrum shows that the DFT formalism, particularly the B3LYP functional, give an accurate description of the isoconazole and bifonazole chemical shifts. Full article

Xeroderma Pigmentosum protein C (XPC) is involved in recognition and repair of bulky DNA damage such as lesions induced by Ultra Violet (UV) radiation. XPC-mutated cells are, therefore, photosensitive and accumulate UVB-induced pyrimidine dimers leading to increased cancer incidence. Here, we performed a high-throughput screen to identify chemicals capable of normalizing the XP-C phenotype (hyper-photosensitivity and accumulation of photoproducts). Fibroblasts from XP-C patients were treated with a library of approved chemical drugs. Out of 1280 tested chemicals, 16 showed ≥25% photo-resistance with RZscore above 2.6 and two drugs were able to favor repair of 6-4 pyrimidine pyrimidone photoproducts (6-4PP). Among these two compounds, Isoconazole could partially inhibit apoptosis of the irradiated cells especially when cells were post-treated directly after UV irradiation while Clemizole Hydrochloride-mediated increase in viability was dependent on both pre and post treatment. No synergistic effect was recorded following combined drug treatment and the compounds exerted no effect on the proliferative capacity of the cells post UV exposure. Amelioration of XP-C phenotype is a pave way towards understanding the accelerated skin cancer initiation in XP-C patients. Further examination is required to decipher the molecular mechanisms targeted by these two chemicals. Full article