Treatment Of Superficial Fungal Infections Research Articles

La eficacia de los aceites ozonizados en el tratamiento de pacientes con micosis superficiales.

Abstract. Superficial mycoses are one of the main reasons for consulta-tion in the dermatological area. In recent years, the therapeutic effectiveness of ozonated oils in fungal infections has been verified in different countries due to its broad germicidal and antifungal spectrum. The objective is to evaluate the efficacy of the use of ozonated sunflower oil in the treatment of superficial mycoses in patients of the Mycology consultation at the Dermatology Service of the Hospital Vargas de Caracas, Instituto Autonómo de Biomedicina “Dr. Ja-cinto Convit”. A cross-sectional descriptive, experimental study was conducted, where 36 patients diagnosed with superficial mycosis and ten healthy subjects were evaluated. Of the group of 36 patients, 26 were treated with ozonated sun-flower oil (AGO) and ten patients with non-ozonized sunflower oil (AGNO). Ten healthy individuals represented the AGO sensitivity control. The most frequent superficial mycosis evaluated in the AGO group was tinea corporis (31%), fol-lowed by denture stomatitis (23%) and for the AGNO group, tinea pedis (50%). Regarding the etiological agent, an improvement with the AGO treatment of 86% for Candida albicans and 60% for the Trichophyton rubrum complex was evidenced at week eight of treatment. It is concluded that the antifungal effect of AGO is more significant for the genus Candida spp than for dermatophytes, evidencing a total improvement of the lesions with six weeks of treatment.

Formulation and Evaluation of Butenafine Hydrochloride-Incorporated Solid Lipid Nanoparticles as Novel Excipients for the Treatment of Superficial Fungal Infections.

The objective of the present study was to develop natural excipient-based solid lipid nanoparticles (SLN) of butenafine hydrochloride (BUTE) using a modified solvent emulsification technique and to evaluate the competence of aloe vera nanolipidgel in enhancing the penetration of BUTE. BUTE-SLNs were prepared using a 23 factorial design to correlate the effect of formulation components on the BUTE-SLN. Particle size, polydispersity index (PDI), zeta potential, entrapment performance, and drug loading were assessed in the formed SLNs. The fabricated BUTE-SLN was evaluated for transmission electron microscopy, fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction study studies and revealed the encapsulation of BUTE in lipid in the amorphous state. BUTE-SLN-based aloe vera gel was formulated and evaluated compared with the marketed product with respect to primary skin irritation, hydration, skin permeation, and antifungal activity. The BUTE-SLN aloe vera gel, optimized for its formulation, features excellent slip properties and controlled drug release. DSC and XRD studies confirm its amorphous nature with effective drug entrapment. The gel provides enhanced skin deposition, improved antifungal activity, and reduced irritation. This makes it a cost-effective and innovative alternative to traditional dosage forms. BUTE-SLN promisingly showed no irritation, higher hydrating potential, slow and sustained release, and enhanced antifungal activity. With an aim to target deeper skin strata, minimize the side effects of drugs and symptomatic impact of fungal infection, and shorten the duration of therapy, BUTE-SLN was successfully prepared. The mean particle size and PDI were 261.25 ± 2.38 nm and 0.268 ± 0.01, respectively. BUTE-SLN gel offers improved topical delivery of BUTE with significantly higher compatibility and antifungal activity than the marketed formulation.

Current Approaches in the Treatment of Superficial Fungal Infections

Current Approaches in the Treatment of Superficial Fungal Infections

Recent progression in nanocarrier based techniques to address fungal infections and patent status in drug development process.

Fungal infections are becoming one of the most common diseases in recent years, especially when it comes about dealing skin infections. Different drugs are available commercially with antifungal activity for topical application and are effective for treatment of mild to moderate fungal infections. However they lack dermal bioavailability due to their poor penetrability, and less retention at the site thereby resulting in poor efficacy. The remaining systemic treatment options available so far may cause adverse drug effects and many other complications. In recent years nano carrier based formulations promised to overcome the limitations of the conventional topical dosage forms. Lipid based nano carriers and their importance for potential use in delivery of antifungal agents for the treatment of superficial fungal infections have been well discussed in this review article. It comprises of different nano lipid systems involved in treatment of topical fungal infections, effect of different polymers on their size, stability, and their mechanistic action behind skin penetration and dermal retention of drug into deeper epidermal layers is also highlighted to depict recent efforts of researchers in this context. Further, the addressing of the disease by novel drug delivery systems for the efficacious treatment, status of clinical trials, novel commercial formulations available for use in dermal drug delivery and patents claimed/granted in the respective field have been discussed in detail.

Current status and research progress of nanoparticle application in superficial fungal infection.

Superficial fungal infections (SFIs) are characterized by diverse etiologies, complex pathogenesis, and marked geographical differences in patient symptoms. Conventional management of SFIs is associated with complications such as hepatotoxicity, skin problems, severe headaches, and clinical difficulties including intractable relapses and drug-drug interactions in patients with chronic diseases remain to be addressed. Moreover, in topical treatment, low penetration of antifungal drugs in hard tissues such as finger (toe) nails and drug-resistant fungi are emerging concerns in current antifungal therapy. Nanotechnology has been a leading research topic in recent years for new dosing forms of antifungal drugs, chemical modification of traditional drugs, and pharmacokinetic improvement, providing potential opportunities for the effective treatment of SFIs. The present study reviewed the direct use of nanoparticles in SFIs and the use of nanoparticles as carriers in SFIs and discussed their future medicinal applications.https://www.europeanreview.org/wp/wp-content/uploads/01-12915-PM-29863.jpg.

Synergistic Interactions between Linalool and Some Antimycotic Agents against Candida spp. as a Basis for Developing New Antifungal Preparations

The incidence of superficial infections, including oral candidiasis, has recently increased significantly. Their treatment is quite difficult due to the growing resistance of Candida spp. to antifungal agents. Therefore, it is necessary to search for novel antimycotics or alternative antifungal therapies. The purpose of the study was to evaluate the antifungal activity of natural terpene—linalool (LIN)—against both reference fungi belonging to yeasts and Candida spp. isolates from the oral cavities of immunocompromised, hemato-oncology patients. Moreover, its mechanism of action and interactions with selected antifungal drugs or antiseptics were investigated. The broth microdilution technique, ergosterol or sorbitol tests, and a checkerboard method were used for individual studies. The LIN showed potential activity toward studied strains of fungi with a minimal inhibitory concentration (MIC) in the range of 0.5–8 mg/mL and fungicidal effect. This compound was also found to bind to ergosterol in the yeast cell membrane. Additionally, the interactions between LIN with antiseptics such as chlorhexidine, cetylpyridinium, and triclosan showed beneficial synergistic effect (with FIC = 0.3125–0.375), or an additive effect with silver nitrate and chlorquinaldol (FIC = 0.625–1). Moreover, statistically significant differences in MIC values were found for the synergistic combinations of LIN. No interaction was indicated for nystatin. These results confirm that the LIN seems to be a promising plant component used alone or in combination with other antimycotics in the prevention and treatment of superficial fungal infections. However, further clinical trials are required.

A "Solution" for Patients Unable to Swallow a Pill: Crushed Terbinafine Mixed With Syrup.

Because oral terbinafine is now formulated only as a tablet, there is a barrier to treatment of superficial fungal infections in patients who are unable to swallow a pill such as young children and patients with pill dysphagia. We describe a preparation method that allows this population to safely and effectively use oral terbinafine.

Treatment of Superficial Mycoses Using Photodynamic Therapy: A Systematic Review and Meta-Analysis.

Objective: The purpose of this study is to evaluate the effectiveness and safety of photodynamic therapy (PDT) in treating superficial fungal infections, and provide reference for clinical application. Methods: In accordance with Population, Intervention, Comparator, and Outcome (PICO), the research question and keywords were formulated. Records published in English by PubMed, Embase, Cochrane Library, and Web of Science as of November 14, 2022 were retrieved, including the keywords "mycoses," "tinea," "photochemotherapy," etc. Besides, meta-analysis performed by STATA and PROSPERO registration code was CRD42022363448. Results: One thousand four hundred eighty-four records were identified and 18 articles involving 343 patients with superficial fungal infections were enrolled. The overall mycological cure rate of PDT is 55% [95% confidence interval (CI): 0.46-0.65]. The fungal cure rate using methylene blue (MB) as photosensitizer (PS) is 67% (95% CI: 0.55-0.79); using 5-aminolevulinic acid is 34% (95% CI: 0.21-0.47); and using methyl aminolevulinate is 56% (95% CI: 0.33-0.78). The fungal cure rate of moderate-to-severe onychomycosis according to Onychomycosis Severity Index is 60% (95% CI: 0.47-0.73) and that of moderate onychomycosis is 66% (95% CI: 0.56-0.76). It was observed that the treatment parameters did not follow the same standard across studies. The majority of the included studies were moderate to low biased. Conclusions: PDT, particularly using MB as PS, has a certain mycological cure rate and safety at treating superficial mycoses. Due to the insufficient number of studies on PDT in the treatment of superficial fungal infections and the small sample size of some studies, more studies with standardized PDT parameters, large sample size, and long follow-up periods are needed to prove that PDT has the potential to become an alternative to traditional antifungal therapy or to find a better combination between them.

Formulation development, optimization, and characterization of anti-fungal topical biopolymeric film using a niosomal approach

Background: Griseofulvin is an antifungal drug that is currently available in the market only in oral dosage forms. So, the development of topical treatment could be advantageous for the treatment of superficial fungal infections. Though for superficial fungal treatment, the skin acts as a major target as well as a principal barrier for drug delivery. To overcome this the colloidal carrier system niosome was used. Niosomes being in the nanometer size range would allow the delivery of the drug at the desired site. Niosomes being non-ionic surfactant-based vehicles would facilitate the passage of the drugs through as skin is composed of both lipid and aqua, which would create problems for any other delivery system. Methodology: Griseofulvin belonging to the BCS Class II was formulated in the form of niosomes to enhance the drug’s solubility. In this study, optimization of niosomal formulation was done using OVAT (one variable at a time) method. Here, the CMAs (critical material attributes) such as surfactant type, conc. of charge inducer and the ratio of surfactant: cholesterol and CPPs (critical processing parameters) such as rotational speed of evaporator flask, external phase temperature, hydration time, and external phase volume (both aqueous and organic), which are independent variables influencing factors at different levels. These are said to have a potential risk on the CQAs (critical quality attributes), which are dependent variables, such as vesicle size, vesicle shape, vesicle lamellarity, niosome aggregation, and drug entrapment efficiency, for the final selection of improved optimum batch. The films were prepared from the incorporation of griseofulvin-loaded optimized niosomes in chitosan film for topical drug delivery in superficial fungal infections. Characterization: The films properties were characterized by physical appearance, film thickness, weight variation, folding endurance, tensile strength, moisture, uptake, moisture content, drug content uniformity, In-vitro drug diffusion studies, ex-vivo studies, and antifungal efficacy against Candida albicans sp. Result and Discussion: Thus, chitosan film formulation integrating griseofulvin-loaded niosomes for topical delivery enhanced the solubility of the drug and avoided the side effects associated with the orally-administered marketed formulation. Conclusion: Biopolymer chitosan exhibited antifungal activity implying enhanced drug efficacy. Therefore, two concepts of using optimized vesicular carrier systems and biopolymeric films have been combined and this topical novel composite film having the potential for griseofulvin delivery to superficial fungal infections has been formulated.

P100 Potent inhibition of dermatophyte fungi by Australian native jarrah honey

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM ObjectivesHoney has been used as a remedy for multiple ailments, and the antibacterial activity of many different floral honeys has been extensively explored. The capacity of honey to inhibit fungi is much less well understood. Here we investigate the inhibition of dermatophyte species by native Australian jarrah honey.MethodsJarrah honey was sourced from beekeepers and commercial suppliers. Artificial honey, made from glucose (22.9%), fructose (20.7%), and sucrose (1.6%), was used to control for osmolarity. Hydrogen peroxide production by honey was assessed using horseradish peroxidase (HRP)/ο‐dianisidine colorimetric test. Dermatophytes included Microsporum canis, M. nanum, Nannizzia gypsea, Trichophyton interdigitale, T. rubrum, and T. tonsurans. Minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) for honey were assessed using CLSI methods. Fluorescent and scanning electron microscopy were used to visualize the effect of honey on fungal conidia and hyphae.ResultsJarrah honey inhibited all of the dermatophyte species with MICs ranging from 1.5-3.5% w/v, and MFCs from 2-5% w/v. No antifungal activity was seen with the artificial honey indicating this was not due to osmolarity. Microscopy revealed honey treatment prevented the germination of conidia and caused hyphae to bulge and collapse. While the inhibitory action of jarrah honey was greatly reduced by the addition of catalase suggesting hydrogen peroxide production was responsible for inhibition and killing, microscopy revealed hyphae were still damaged suggesting there are agents within honey that augment antifungal activity. REDOX fluorophores failed to detect internal oxidative stress within hyphae, indicating that damage likely occurs on the hyphal surface.ConclusionJarrah honey is a non-toxic agent that may have utility in the treatment of superficial fungal infections caused by dermatophyte fungal species.

Pharmacokinetics of fluconazole after oral administration to healthy beagle dogs

Fluconazole can be effective in the treatment of superficial mycoses in dogs. However, the pharmacokinetics of fluconazole have not yet been evaluated to determine its optimal dosing regimen. This study aimed to determine the plasma concentration of fluconazole after single and multiple administrations at two different dosages in dogs. Eight healthy beagle dogs were divided into two groups, and each group received either 5 or 10mg/kg of fluconazole per os. The pharmacokinetics of fluconazole was determined following single and multiple administrations p.o. Single- and multiple-dose treatment periods were separated by a washout period of seven days. Plasma concentrations of fluconazole were determined by established high-performance liquid chromatography coupled with tandem mass spectrometry system. In the 5mg/kg group, the mean maximum concentrations (Cmax ) and the area under the plasma concentrations (AUC0-24h ) were 4.84 μg/mL and 85.56 μg*h/mL, respectively, after single administration and 6.58 μg/mL and 119.52 μg*h/mL, respectively, after multiple administrations. In the 10mg/kg group, the Cmax and AUC0-24h were 5.67 μg/mL and 109.19 μg*h/mL, respectively, after single administration and 15.10μg/mL and 291.51 μg*h/mL, respectively, after multiple administrations. The Cmax (p< 0.001) and AUC0-24h (p< 0.001) were significantly lower in the 5mg/kg group than those in the 10mg/kg group at multiple administrations. Fluconazole accumulates in plasma and exhibits dose-proportional pharmacokinetics after multiple doses, and was safe and well tolerated at these doses for short-term administration.

Discovery of evodiamine derivatives as potential lead antifungal agents for the treatment of superficial fungal infections

Mycosis, especially superficial fungal infections (SFIs), has been a serious threat to humans in recent years. Evodiamine (EVO), as an effective component of the Traditional Chinese Medicine Evodia rutaecarpa, has good antibacterial effects and low toxicity. In order to find out the potential therapeutic agents against SFIs, a series of EVO derivatives were synthesized and systematic evaluations of antifungal activity were carried out. Among them, compound A7 exhibited great antifungal activity with the values of MIC100 were 38, 38 and 2 μg/mL, respectively, against T. rubrum, T. mentagrophytes and C. albicans, and even stronger than that of ketoconazole (KCZ) with the values of MIC100 were 106, 106 and 3 μg/mL, respectively. Further antifungal evaluations in vitro verified that compound A7 indeed had favorable antifungal activity. Moreover, compound A7 could exert excellent antifungal effect on T. rubrum-infected guinea pigs, suggesting that A7 was an attractive molecule and could be a potential lead compound for the development of anti-fungal agents, and providing a great promising therapeutic strategy for fungal disease.

The use of fluconazole in the treatment of superficial fungal infections- A meta-analysis

The study evaluated the efficacy of the once-weekly dose of oral fluconazole 150 mg therapy in dermatophytosis in comparison to placebo or comparator in the adult patient. A systematic literature search was conducted to identify relevant studies published from 2011 until March 2021. Two reviewers independently abstracted data and assessed study quality. Oral fluconazole 150 mg tablet per week is effective in reducing dermatophytosis after 4 weeks (OR 0.14 95% Cl -1.81-1.82). The heterogenicity test shows no substantial changes between the two studies included in the meta-analysis (Chi=2.36, df=1, I=56.68%; P=0.124). Weekly treatment of fluconazole 150 mg by oral route for 4 weeks is effective against dermatophytosis.

Luliconazole Topical Dermal Drug Delivery for Superficial Fungal Infections: Penetration Hurdles and Role of Functional Nanomaterials.

Luliconazole is the first and only anti-fungal agent approved for the short-term treatment of superficial fungal infections. However, commercially available conventional topical dermal drug delivery cargo of luliconazole is associated with certain limitations, like lower skin permeation and shorter skin retention of drug. Therefore, the present review is an attempt to unravel the penetration hurdles in luliconazole topical dermal drug delivery. Moreover, we have also summarized the activity of functional nanomaterials-based drug delivery systems employed by the scientific fraternity to improve luliconazole efficacy in superficial fungal infections on a case-to-case basis. In addition, efforts have also been made to unveil the critically acclaimed mechanism of action of luliconazole against fungal cells. Under the framework of future prospects, we have analyzed the combination of luliconazole with isoquercetin using the in-silico docking technique for offering synergistic antifungal activity. Isoquercetin exhibited a good affinity for superoxide dismutase (SOD), a fungal target, owing to the formation of hydrogen bonds with Glu132, Glu133, and Arg143, in addition to a few hydrophobic interactions. On the other hand, luliconazole inhibited lanosterol-14α-demethylase, and consequently blocked ergosterol. In addition, nanotechnology and artificial neural network (ANN) derived integrated drug delivery systems may also be explored for augmenting the luliconazole therapeutic efficacy in topical fungal infections. Synergy of ANN models along with topical nanoscaled drug delivery may help to achieve critical quality attributes (CQA), leading to commercial success of luliconazole.

Developing a new treatment for superficial fungal infection using antifungal Collagen-HSAF dressing.

Fungal pathogens are common causes of superficial clinical infection. Their increasing drug resistance gradually makes existing antifungal drugs ineffective. Heat stable antifungal factor (HSAF) is a novel antifungal natural product with a unique structure. However, the application of HSAF has been hampered by very low yield in the current microbial producers and from extremely poor solubility in water and common solvents. In this study, we developed an effective mode of treatment applying HSAF to superficial fungal infections. The marine‐derived Lysobacter enzymogenes YC36 contains the HSAF biosynthetic gene cluster, which we activated by the interspecific signaling molecule indole. An efficient extraction strategy was used to significantly improve the purity to 95.3%. Scanning electron microscopy images revealed that the Type I collagen‐based HSAF (Col‐HSAF) has a transparent appearance and good physical properties, and the in vitro sustained‐release effect of HSAF was maintained for more than 2 weeks. The effective therapeutic concentration of Col‐HSAF against superficial fungal infection was explored, and Col‐HSAF showed good biocompatibility, lower clinical scores, mild histological changes, and antifungal capabilities in animals with Aspergillus fumigatus keratitis and cutaneous candidiasis. In conclusion, Col‐HSAF is an antifungal reagent with significant clinical value in the treatment of superficial fungal infections.

The March Against Onychomycosis: A Systematic Review of the Sanitization Methods for Shoes, Socks, and Textiles.

Drug-based treatment of superficial fungal infections, such as onychomycosis, is not the only defense. Sanitization of footwear such as shoes, socks/stockings, and other textiles is integral to the prevention of recurrence and reduction of spread for superficial fungal mycoses. The goal of this review was to examine the available methods of sanitization for footwear and textiles against superficial fungal infections. A systematic literature search of various sanitization devices and methods that could be applied to footwear and textiles using PubMed, Scopus, and MEDLINE was performed. Fifty-four studies were found relevant to the different methodologies, devices, and techniques of sanitization as they pertain to superficial fungal infections of the feet. These included topics of basic sanitization, antifungal and antimicrobial materials, sanitization chemicals and powder, laundering, ultraviolet, ozone, nonthermal plasma, microwave radiation, essential oils, and natural plant extracts. In the management of onychomycosis, it is necessary to think beyond treatment of the nail, as infections enter through the skin. Those prone to onychomycosis should examine their environment, including surfaces, shoes, and socks, and ensure that proper sanitization is implemented.

Characterization and Antidermatophyte Activity of Henna Extracts: A Promising Therapy for Humans and Animals Dermatophytoses.

Dermatophytoses representing a major global health problem and dermatophyte species with reduced susceptibility to antifungals are increasingly reported. Therefore, we investigated for the first time the antidermatophyte activity and phytochemical properties of the sequential extracts of the Egyptian privet Henna (Lawsonia inermis) leaves. Total phenolic content (TPC), total flavonoids(TF), and antioxidant activity of chloroform, diethyl ether, acetone, ethanol 80%, and aqueous extracts were evaluated. The antifungal activity of henna leaves extracts (HLE) toward 30 clinical dermatophytes isolates, including Trichophyton mentagrophytes, Microsporum canis, and T. rubrum, was determined. Morphological changes in hyphae were investigated using scanning electron microscopy (SEM) analysis. Following the polarity of ethanol and acetone, they exhibited distinct efficiency for the solubility and extraction of polyphenolic polar antioxidants from henna leaves. Fraxetin, lawsone, and luteolin-3-O-glucoside were the major phenolic compounds of henna leaves, as assessed using high-performance liquid chromatography analysis. A high and significant positive correlation was found between TPC, TF, the antioxidants, and the antidermatophyte activities of HLE. Acetone and ethanol extracts exhibited the highest antifungal activity toward the tested dermatophyte species with minimum inhibitory concentration (MIC) ranges 12.5-37.5 and 25-62.5µg/mL, respectively. Structural changes including collapsing, distortion, inflating, crushing of hyphae with corrugation of walls, and depressions on hyphal surfaces were observed in SEM analysis for dermatophyte species treated with MICs of griseofulvin, acetone, and ethanol extracts. In conclusion, acetone and ethanolic extracts of henna leaves with their major constituent fraxetin exhibited effective antifungal activity toward dermatophyte species and may be developed as an alternative for dermatophytosis treatment. These findings impart a useful insight into the development of an effective and safe antifungal agent for the treatment of superficial fungal infections caused by dermatophytes.

Antifungal Drug Resistance of Dermatophytes Causing Superficial Fungal Infections

Background: Superficial fungal infections (SFI) are common skin diseases that were largely simple to treat. However, due to increasing antimicrobial resistance (AMR) of dermatophytes to antifungal drugs, treatment of SFI has become difficult. This study aims to analyze the AMR of dermatophytes and to correlate with the clinical response of antifungal drugs. Methods: A cross‑sectional evaluation was undertaken of 570 consecutive patients with SFI such as tinea corporis, tinea cruris, tinea faciei, and tinea pedis, who were treated with any of the oral antifungal drugs fluconazole, itraconazole and terbinafine. Clinical response was taken within 1 month of stopping the therapy. Microscopic as well as culture and antimicrobial sensitivity analysis were done to characterize and determine the susceptibility of dermatophytes to antifungal drugs aforementioned. Results: Among the 570 patients with SFI, the ratio of male (n=360, 63.16%) to female (n=210, 36.84%) was 1.7:1. The common age group affected by SFI was 31-40 years (27.71%, n=158). The tinea corporis was the most predominant (51.05%) followed by tinea cruris (13.68%). Clinical response analysis showed that the percentage of relapse of SFI after completion of treatment with fluconazole, itraconazole and terbinafine was about 55, 45 and 19, respectively. Culture and antimicrobial sensitivity analysis revealed that the percentage of resistance of dermatophytes from patients of SFI to fluconazole, itraconozole and terbinafine was approximately 70, 55 and 20, respectively. Conclusion: Results reported herein support the notion that the antifungal resistance is evolving in dermatophytes causing SFI, and about 20% dermatophytes are multidrug resistant.

Development and Optimization of Itraconazole-Loaded Solid Lipid Nanoparticles for Topical Administration Using High Shear Homogenization Process by Design of Experiments: In Vitro, Ex Vivo and In Vivo Evaluation.

The aim of present study was to develop topical itraconazole (ITZ)-loaded solid lipid nanoparticles for treatment of superficial fungal infections. Formulations were prepared using high shear homogenization process, and optimized by employing a two-step design of experiments (DoE) approach. It comprised a Taguchi experimental design for screening of 'vital few' factors, and a central composite experimental design for optimization. Overlay of the response surface maps for percent drug entrapment (PDE), particle size, ITZ skin retention and permeation was performed to obtain the optimized ITZ-loaded SLNs (OPT-SLNs) suspension. The optimized ITZ-loaded SLNs (OPT-SLNs) showed mean particle size of (262.92 ± 8.56nm) and zeta potential value of 22.36mV. Excellent drug entrapment (94.21 ± 3.35%) and skin retention of ITZ (43.03 ± 1.86μg/cm2) was achieved by OPT-SLNs. The hydrogel formulation of OPT-SLNs exhibited good gel consistency and spreadability characteristics. Pharmacodynamic and skin sensitivity studies in standardized rodent models revealed that OPT-SLNs hydrogel was more efficacious than conventional oral and topical antifungal therapies, and also safe for topical administration. Furthermore, the histoptahological evaluation depicted complete recovery of infected rats after 14-day treatment regimen of OPT-SLNs hydrogel. The developed formulation was found to have tremendous potential to enhance ITZ activity through topical administration approach.

Aloe-emodin-mediated antimicrobial photodynamic therapy against dermatophytosis caused by Trichophyton rubrum.

Summary Trichophyton rubrum is responsible for the majority of dermatophytosis. Current systemic and topical antifungals against dermatophytosis are often tedious and sometimes unsatisfactory. Antimicrobial photodynamic therapy (aPDT) is a non‐invasive alternative suitable for the treatment of superficial fungal infections. This work investigated the photodynamic inactivation efficacy and effects of aloe‐emodin (AE), a natural photosensitizer (PS) against T. rubrum microconidia in vitro, and evaluated the treatment effects of AE‐mediated aPDT for T. rubrum‐caused tinea corporis in vivo and tinea unguium ex vivo. The photodynamic antimicrobial efficacy of AE on T. rubrum microconidia was evaluated by MTT assay. The inhibition effect of AE‐mediated aPDT on growth of T. rubrum was studied. Intracellular location of AE, damage induced by AE‐mediated aPDT on cellular structure and surface of microconidia and generation of intracellular ROS were investigated by microscopy and flow cytometry. The therapeutic effects of AE‐mediated aPDT against dermatophytosis were assessed in T. rubrum‐caused tinea corporis guinea pig model and tinea unguium ex vivo model. AE‐mediated aPDT effectively inactivated T. rubrum microconidia in a light energy dose‐dependent manner and exhibited strong inhibitory effect on growth of T. rubrum. Microscope images indicated that AE is mainly targeted to the organelles and caused damage to the cytoplasm of microconidia after irradiation through generation of abundant intracellular ROS. AE‐mediated aPDT demonstrated effective therapeutic effects for T. rubrum‐caused tinea corporis on guinea pig model and tinea unguium in ex vivo model. The results obtained suggest that AE is a potential PS for the photodynamic treatment of dermatophytosis caused by T. rubrum, but its permeability in skin and nails needs to be improved.