Delving into the Latest Updates on Isoconazole Nitrate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Isoconazole, Isoconazole nitrate (JAN), R-15454

+ [12]

Target

CYP2C9

Mechanism

CYP2C9 inhibitors(Cytochrome P450 2C9 inhibitors)

Therapeutic Areas

Infectious DiseasesSkin and Musculoskeletal DiseasesUrogenital Diseases

Active Indication

Skin Diseases, InfectiousVaginitisCandidiasis+ [1]

Inactive Indication

Candidiasis, VulvovaginalOnychomycosis

Originator Organization

Bayer Yakuhin Ltd.

Active Organization

Bayer Yakuhin Ltd.

Inactive Organization

Abeona Therapeutics, Inc.Shenyang Huatai Medication Research Co., Ltd.

Drug Highest PhaseApproved

First Approval Date

JP (16 Jun 1982),

CandidiasisMycoses

Regulation-

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Structure

Molecular FormulaC18H15Cl4N3O4

InChIKeyNNGQLSIGRSTLLU-UHFFFAOYSA-N

CAS Registry24168-96-5

Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate (ODHP) was extracted in a previous study from the culture broth of soil isolate Alcaligenes faecalis MT332429 and showed a promising antimycotic activity. This study was aimed to formulate ODHP loaded β-cyclodextrins (CD) nanosponge (NS) hydrogel (HG) to control skin fungal ailments since nanosponges augment the retention of tested agents in the skin. Box-Behnken design was used to produce the optimized NS formulation, where entrapment efficiency percent (EE%), polydispersity index (PDI), and particle size (PS) were assigned as dependent parameters, while the independent process parameters were polyvinyl alcohol % (w/v %), polymer-linker ratio, homogenization time, and speed. The carbopol 940 hydrogel was then created by incorporating the nanosponges. The hydrogel fit Higuchi’s kinetic release model the best, according to in vitro drug release. Stability and photodegradation studies revealed that the NS-HG remained stable under tested conditions. The formulation also showed higher in vitro antifungal activity against Candida albicans compared to the control fluconazole. In vivo study showed that ODHP-NS-HG increased survival rates, wound contraction, and healing of wound gap and inhibited the inflammation process compared to the other control groups. The histopathological examinations and Masson’s trichrome staining showed improved healing and higher records of collagen deposition. Moreover, the permeability of ODHP-NS-HG was higher through rats’ skin by 1.5-folds compared to the control isoconazole 1%. Therefore, based on these results, NS-HG formulation is a potential carrier for enhanced and improved topical delivery of ODHP. Our study is a pioneering research on the development of a formulation for ODHP produced naturally from soil bacteria.

Key points:

• Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate was successfully formulated as a nanosponge hydrogel and statistically optimized.• The new formula exhibited in vitro good stability, drug release, and higher antifungal activity against C. albicans as compared to the fluconazole.• Ex vivo showed enhanced skin permeability, and in vivo analysis showed high antifungal activity as evidenced by measurement of various biochemical parameters and histopathological examination.

01 Dec 2024·Antonie van Leeuwenhoek

Species distribution and antifungal susceptibility profiles of yeasts isolated from onychomycosis: a cross-sectional study with insights into emerging species

Article

Author: Shariat, Sahar ; Motamedi, Marjan ; Rezaei Arab, Maryam ; Jabrodini, Ahmad ; Yazdanpanah, Somayeh ; Zomorodian, Kamiar ; Ghasemi, Farnia ; Kharazi, Mahboobeh ; Shabanzadeh, Shafigheh

Candida onychomycosis is a common fungal infection affecting the nails, primarily caused by Candida (C.) species. Regarding the increasing trend of Candida onychomycosis and the antifungal resistant phenomenon in recent years, this study aims to evaluate the epidemiological characteristics of Candida onychomycosis, the distribution of emerging species, and the antifungal susceptibility profiles of isolates. Onychomycosis caused by yeast species was confirmed through direct examination and culture of nail scraping among all individuals suspected to have onychomycosis and referred to a medical mycology laboratory between June 2019 and March 2022. Species of yeast isolates were identified using the multiplex PCR and PCR-RFLP methods. The antifungal susceptibility of isolates to common antifungal agents and imidazole drugs was evaluated according to the M-27-A3 CLSI protocol. Among 101 yeast strains isolated from onychomycosis, Candida parapsilosis complex (50.49%) was the most common species, followed by C. albicans (20.79%) and C. tropicalis (10.89%). Rare species of yeasts such as C. guilliermondii and Saccharomyces cerevisiae were also identified by molecular methods. Results obtained from antifungal susceptibility testing showed significant differences in MIC values of isoconazole, fenticonazole, and sertaconazole among different species. Overall, a fluconazole-resistant rate of 3% was found among Candida species. Moreover, there was a statistically significant difference in MICs of fenticonazole and clotrimazole between the two most prevalent causative species, C. parapsilosis complex and C. albicans. Correct identification of the causative agents of onychomycosis and performing susceptibility testing could be helpful in choosing the most appropriate antifungal therapy.

01 Dec 2024·FUNDAMENTAL & CLINICAL PHARMACOLOGY

Nociceptive TRP channels function as molecular target for several antifungal drugs

Article

Author: Takahashi, Kenji ; Ohta, Toshio ; Okabe, Shota ; Hashimoto, Miho

Abstract:

Background/objectives:

Topically applied antifungal agents can induce adverse effects, such as pain and irritation. The transient receptor potential (TRP) channels—TRPA1 and TRPV1—mainly expressed in sensory neurons, act as sensors for detecting irritants. This study aims to evaluate the involvement of nociceptive channels in topical antifungal‐induced pain and irritation. We tested nine topical antifungals belonging five classes: isoconazole, econazole, miconazole, clotrimazole, and ketoconazole as imidazoles; liranaftate as a thiocarbamate; terbinafine as an allylamine; amorolfine as a morpholine; and butenafine as a benzylamine.

Methods:

Intracellular calcium concentrations ([Ca2+]i) and membrane currents in response to antifungals were measured to estimate channel activity using heterologously expressing cells and isolated mouse sensory neurons.

Results:

In mouse TRPA1‐expressing cells, all the tested drugs induced an increase in [Ca2+]i, which was abrogated or reduced by a TRPA1 blocker. Although many drugs evoked the TRPA1‐nonspecific [Ca2+]i response at high concentrations, responses to clotrimazole, ketoconazole, and liranaftate were TRPA1 specific and elicited current responses in TRPA1‐expressing cells. In mouse TRPV1‐expressing cells, clotrimazole and ketoconazole elicited [Ca2+]i and current responses. In mouse sensory neurons, liranaftate‐induced increase in [Ca2+]i was abrogated by a TRPA1 blocker and Trpa1 deletion. Responses to ketoconazole were inhibited by TRPA1 and TRPV1 blockers and by the genetic deletion of either channel.

Conclusion:

These results suggest that topical antifungal‐induced pain and irritation are attributable to the activation of nociceptive TRPA1 and/or TRPV1 channel/s. Consequently, caution should be exercised in the use of topical antifungals with symptoms of pain.

100 Deals associated with Isoconazole Nitrate

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