In vitro determination of the combination of ciclopirox and terbinafine in the treatment of dermatophytosis.

INTRODUCTION: The cases of dermatophytosis are increasing and they are associated with a higher number of therapeutic failures leading the doctor to prescribe combinations of antifungals as therapy. The objective was to evaluate the interaction of terbinafine and ciclopirox, the most commonly antifungals used in the clinic, in dermatophyte isolates. METHODOLOGY: The minimum inhibitory concentrations (MIC) of ciclopirox and terbinafine were determined by the broth microdilution method according CLSI and the checkerboard assay was used to evaluate the interaction between the antifungal agents. RESULTS: For terbinafine the mic50 was 0.125 ug/mL and mic90 was 0.250 ug/mL. For ciclopirox the values were 2.0 ug/mL for mic50 and 4.0 ug/mL for mic90. No synergistic interaction was observed for the dermatophyte isolates tested. CONCLUSION: These results suggest that the use of terbinafine in combination with ciclopirox, which is widely used in the clinic, may not be a good choice for the treatment of onychomycosis.

Rose bengal-encapsulated chitosan nanoparticles for the photodynamic treatment of Trichophyton species.

Rose bengal (RB) solutions coupled with a green laser have proven to be efficient in clearing resilient nail infections caused by Trichophyton rubrum in a human pilot study and in extensive in vitro experiments. Nonetheless, the RB solution can become diluted or dispersed over the tissue and prevented from penetrating the nail plate to reach the subungual area where fungal infection proliferates. Nanoparticles carrying RB can mitigate the problem of dilution and are reported to effectively penetrate through the nail. For this reason, we have synthesized RB-encapsulated chitosan nanoparticles with a peak distribution size of ~200 nm and high reactive oxygen species (ROS) production. The RB-encapsulated chitosan nanoparticles aPDT were shown to kill more than 99% of T. rubrum, T. mentagrophytes, and T. interdigitale spores, which are the common clinically relevant pathogens in onychomycosis. These nanoparticles are not cytotoxic against human fibroblasts, which promotes their safe application in clinical translation.

Development by design of experiment and validation of a HPLC-UV method for simultaneous quantification of 1-nitro-2-phenylethane and methyleugenol: Application to nail permeation/retention studies.

Aniba canelilla (Kunth) Mez is an aromatic tree from Amazon region whose essential oil presents 1-nitro-2-phenylethane (NP) and methyleugenol (ME) as major compounds. Several properties are attributed to Aniba canelilla essential oil (ACEO), such as antifungal. Onychomycoses are fungal nail infections that require novel therapeutic alternatives, especially topical ones. However, to ensure the success of topical therapy, the active compound should be able to penetrate/permeate the nail plate, which is challenging due to the highly keratinized composition of this structure. Thus, the aims of this article were to develop, validate and apply a high-performance liquid chromatography method (HPLC-UV) to quantify NP and ME in porcine hoof extract (PHE) and receptor fluid (RF) during in vitro permeation/retention studies in nail model, for which porcine hoof membranes were used. For method development, two Designs of Experiment (DoE) were adopted: 23 Full Factorial and Box-Behnken. Retention times of 5.65 and 7.49 min were achieved for NP and ME, respectively. The method was full validated for NP and ME quantification in receptor fluid, in accordance with the recommended parameters by ICH Q2(R1) Guideline. In addition, the method was full validated for NP and ME quantification in porcine hoof extract, considering the parameters and criteria of ICH M10 Guideline. In vitro permeation/retention studies were carried out in nail model, and promising results were obtained. NP reached the receptor fluid in the order of 441.1 ± 92.1 µg/cm2 at 72 h. The amount of NP and ME retained into porcine hoof membrane was 1272.6 ± 225.7 µg/cm2 and 84.7 ± 20.4 µg/cm2, respectively, at 72 h. Our findings open perspective to develop topical formulations containing ACEO as active compound aiming the management of onychomycosis.

Photodynamic inactivation by hypericin-P123 on azole-resistant isolates of the Trichophyton rubrum complex as planktonic cells and biofilm.

INTRODUCTION: The Trichophyton rubrum complex comprises the majority of dermatophyte fungi (DM) responsible for chronic cases of onychomycosis, which is treated with oral or topical antifungals. However, owing to antifungal resistance, alternative therapies, such as photodynamic therapy (PDT), are needed. This study investigated the frequency of the T. rubrum species complex in onychomycosis cases in the northwestern region of Paraná state, Brazil, and evaluated the efficacy of (PDT) using P123-encapsulated hypericin (Hyp-P123) on clinical isolates of T. rubrum in the planktonic cell and biofilm forms. MATERIAL AND METHODS: The frequency of the T. rubrum complex in onychomycosis cases from 2017 to 2021 was evaluated through a data survey of records from the Laboratory of Medical Mycology (LEPAC) of the State University of Maringa (UEM). To determine the effect of PDT-Hyp-P123 on planktonic cells of T. rubrum isolates, 1 × 105 conidia/mL were treated with ten different concentrations of Hyp-P123 and then irradiated with 37.8 J/cm2. Antibiofilm activity of PDT-Hyp-P123 was tested against T. rubrum biofilm in the adhesion phase (3 h), evaluated 72 h after irradiation (37.8 J/cm2), and the mature biofilm (72 h), evaluated immediately after irradiation. In this context, three different parameters were evaluated: cell viability, metabolic activity and total biomass. RESULTS: The T. rubrum species complex was the most frequently isolated DM in onychomycosis cases (approximately 80 %). A significant reduction in fungal growth was observed for 75 % of the clinical isolates tested with a concentration from 0.19 µmol/L Hyp-P123, and 56.25 % had complete inhibition of fungal growth (fungicidal action); while all isolates were azole-resistant. The biofilm of T. rubrum isolates (TR0022 and TR0870) was inactivated in both the adhesion phase and the mature biofilm. CONCLUSION: PDT-Hyp-P123 had antifungal and antibiofilm activity on T. rubrum, which is an important dermatophyte responsible for onychomycosis cases.

Individual Article: Updated Review of Topical Pharmaceuticals and Complementary and Alternative Medications for the Treatment of Onychomycosis in Both General and Special Populations in the United States.

Onychomycosis is a prevalent condition affecting the United States and global population. Treatment options are limited, with only 3 topical anti-fungal medications garnering approval in the US within the last 25 years: ciclopirox, tavaborole, and efinaconazole. The economic impact and quality of life burden due to onychomycosis are high. Here we provide an up-to-date review of all approved topical anti-fungal therapies for toenail onychomycosis. We discuss treatment efficacies, pharmacology, and use in special populations, as well as current evidence for complementary and alternative medicine.  J Drugs Dermatol. 2023;22:9(Suppl 1):s5-10.

Strategies to improve the diagnosis and clinical treatment of dermatophyte infections.

INTRODUCTION: Significant problems are associated with the diagnosis and treatment of dermatophyte infections, which constitute the most common fungal infections of the skin. Although this is a common problem in the community, there are no adequate guidelines for the management of all forms of dermatophyte infections. Even if dermatophytes are correctly diagnosed, they sometimes exhibit poor susceptibility to several antifungal compounds. Therefore, long-term treatment may be needed, especially in immunosuppressed patients, for whom antifungal pharmacotherapy may be inconvenient owing to allergies and undesirable drug interaction-related effects. AREAS COVERED: In this review article, problems related to the diagnosis and treatment of dermatophyte infections have been discussed, and suggestions to resolve these problems have been presented. EXPERT OPINION: Pretreatment microscopic or mycological examinations should be performed for dermatophyte infections. In treatment-refractory cases, antifungal-resistant strains should be determined using antifungal susceptibility testing or via molecular methods. Natural herbal, laser, and photodynamic treatments can be used as alternative treatments in patients who cannot tolerate topical and systemic antifungal treatments.

Laserterapia e tratamento medicamentoso tópico na onicomicose em pessoas com diabetes: série de casos* / Terapia láser y tratamiento con medicamento tópico para onicomicosis en personas con diabetes: serie de casos / Laser therapy and topical drug treatment for onychomycosis in people with diabetes: A case-series study

Objetivo: descrever os efeitos da laserterapia de baixa intensidade e do tratamento medicamentoso tópico da onicomicose em pessoas com diabetes. Método: estudo quantitativo, do tipo série de casos. Os participantes foram 21 pessoas com diabetes divididas em dois grupos, sendo o primeiro tratado com laser e o segundo com medicamento tópico no período de outubro de 2020 a agosto de 2021. Os dados foram coletados em histórico e exame clínico das lâminas ungueais e organizados em banco de dados, cuja análise ocorreu por meio de estatística descritiva. Resultados: identificou-se que no grupo I 30% das lâminas ungueais obtiveram cura clínica e no II 26%. Ao avaliar a resposta satisfatória o grupo I apresentou 63% e o II 53%. Conclusão: o tratamento da onicomicose com laserterapia apresentou maior prevalência de resposta satisfatória e cura clínica do que o tratamento medicamento tópico.

Objective: to describe the effects of low-level laser therapy and of topical drug treatment for onychomycosis in people with diabetes. Method: a qualitative study of the case-series type. The participants were 21 individuals with diabetes divided into two groups, the first treated with laser and the second with topical medication from October 2020 to August 2021. The data were collected in a clinical history and examination of the nail plates and organized in a database, whose analysis took place through descriptive statistics. Results: it was identified that 30% and 26% of the nail plates attained clinical cure in groups I and II, respectively. When assessing the satisfactory response, groups I and II presented 63% and 53%, respectively. Conclusion: the onychomycosis treatment with laser therapy presented higher prevalence of satisfactory response and clinical cure than the topical drug treatment.

Objetivo: describir los efectos de la Terapia Láser de Baja Intensidad y del tratamiento con medicamento tópico para la onicomicosis en personas con diabetes. Método: estudio cuantitativo del tipo serie de casos. Los participantes fueron 21 personas con diabetes divididas en dos grupos: el primero tratado con láser y el segundo con un medicamento tópico entre octubre de 2020 y agosto de 2021. Los datos se recolectaron de las historias y los exámenes clínicos de las placas ungueales y se los organizó en una base de datos, cuyo análisis se realizó por medio de estadística descriptiva. Resultados: se identificó que el 30% y el 26% de las placas ungueales alcanzaron cura clínica en los grupos I y II, respectivamente. Al evaluar la respuesta satisfactoria, los grupos I y II presentaron 63% y 53%. Conclusión: el tratamiento de la onicomicosis con terapia láser presentó mayor prevalencia de respuestas satisfactoria y cura clínica que el tratamiento con predicamento tópico.

Fractional CO2 laser - assisted methylene blue photodynamic therapy is a potential alternative therapy for onychomycosis in the era of antifungal resistance.

BACKGROUND: Treatment of onychomycosis is challenging by virtue of the impact of nail disfigurement, the location of the fungi within the nail and reported antifungal resistance worldwide. Light-based technologies are promising primary or adjunctive therapeutic modalities. We aimed to compare the efficacy of photodynamic therapy and fractional CO2 laser monotherapy either alone or in combination for onychomycosis. PATIENTS AND METHODS: This prospective randomized comparative study was conducted on 51 onychomycosis patients divided into three groups. In group A, patients were treated using 6 photodynamic therapy sessions using methylene blue and IPL (560 to 700 nm, fluence 12 J/cm2). Group B patients were treated using 6 bimonthly fractional CO2 laser sessions (10,600 nm, 1.600 mj energy and 0.6 mm density) and group C patients were treated using 6 combined fractional CO2 laser and photodynamic therapy sessions. Patients were evaluated mycologically, dermoscopically and clinically by calculation of proximal nail diameter percentage at baseline, monthly, at the end of treatment and after a 6-month follow-up period post-treatment. RESULTS: Candida was the most commonly isolated organismin in 64.7%, 70.6% and 70.6% of the pateints in groups A, B and C, respectively. The dermoscopic findings in the total dystrophic onychomycosis was subungual hyperkeratosis in 6 patients (100%), longitudinal streaks and striae in 1 patient (16.7%). In dorsolateral subungual onychomycosis, jagged proximal edge in 31 patients (70.5%), and pigmentation in 30 patients (68.2%) were noted. In proximal subungual onychomycosis irregular matt patches were seen in 1 patient (100%). Proximal nail diameter percentage showed statistically significant improvement after treatment and 6 months follow up in the 3 studied groups. Mean increase of proximal nail diameter after treatment was highest in group C (52.94 ± 20.24), followed by group B (43.82 ± 21.03) and least in group A (35.29 ± 17.0). This difference was statistically significant (p = 0.044). Reported side effects were mild-moderate pain, discoloration and paronychia. CONCLUSION: We conclude that fractional CO2 laser and photodynamic monotherapy, and their combination achieve high success rates, good patient satisfaction and safety profile. Fractional CO2-assisted photodynamic therapy is associated with the highest improvement over either fractional CO2 or photodynamic therapy alone.

Bacterial nanocellulose patches as a carrier for hydrating formulations to improve the topical treatment of nail diseases.

Bacterial nanocellulose has been widely investigated for wound healing applications, mainly due to its moisturizing capabilities and biocompatibility. Even though the topical therapy of nail diseases could benefit from these properties, this application has not yet been investigated. Therefore, actively hydrating nail patches based on bacterial nanocellulose were developed to improve the delivery of ciclopirox olamine and Boswellia serrata extract through the nail plate. The nanocellulose matrix was used to enable the application of hydration enhancing solutions based on glycerol and urea as a mechanically stable patch. While the favorable mechanical characteristics of the material remained unchanged, an increase of the incorporated glycerol concentration enhanced the transparency and wetting capacity of the patches. A biphasic drug release from the patches could be observed for drug and extract with a faster release for the hydrophilic ciclopirox olamine. High glycerol concentrations correlated with increased cumulative release and permeation through keratin films for drug and extract, demonstrating the hydration driven permeation enhancement. Patches containing ciclopirox olamine showed strong antimycotic effects against relevant pathogens for onychomycosis. The present finding proposed the combination of bacterial nanocellulose with glycerol, urea and different drug as a promising platform for the local treatment of nail diseases.

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.

Efficacy of laser therapy combined with topical antifungal agents for onychomycosis: a systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: Onychomycosis is a common fungal infection of the nail. Laser and topical antifungal agent combination therapy is an emerging treatment for onychomycosis. The objective of this study was to systematically evaluate the efficacy and safety of laser and topical antifungal agent combination therapy for onychomycosis. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang and VIP databases were searched from inception to November 2021. Randomised controlled trials (RCTs) on laser therapy combined with topical antifungal agents for onychomycosis were included. The Cochrane Collaboration tool was used to assess the risk of bias, and Revman 5.3 software was used in the meta-analysis. RESULTS: Twelve studies involving 869 patients were included in this meta-analysis. The results showed that compared with topical antifungal agents alone, laser and topical antifungal agent combination therapy was superior in terms of the complete cure rate (RR 6.04,95% CI (2.17, 16.85), P = 0.0006), mycological cure rate (RR 1.27, 95% CI (1.10, 1.48), P = 0.001), clinical effective rate (RR 1.38, 95% CI (1.20, 1.57), P < 0.00001) and patient satisfaction rate (RR 1.47,95% CI (1.17, 1.84), P = 0.0009).The subgroup analysis of outcome indicators, including mycological cure rate and clinical effective rate, demonstrated that both carbon dioxide (CO2) laser therapy combined with topical antifungal therapy and 1064-nm neodymium-doped:yttrium aluminium garnet (Nd:YAG) laser therapy combined with topical antifungal therapy showed better results than topical antifungal therapy alone. No adverse events were identified except for three studies reporting transient burning sensation without treatment and mild to moderate pain, both of which were well tolerated. CONCLUSION: The present study indicated that laser and topical antifungal agent combination therapy is effective for onychomycosis. However, more large-scale and well-designed RCTs are warranted.

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

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.

Review of the alternative therapies for onychomycosis and superficial fungal infections: posaconazole, fosravuconazole, voriconazole, oteseconazole.

Terbinafine and itraconazole are the most commonly used oral antifungals to treat onychomycosis and superficial dermatomycoses. Recently, poor response to oral terbinafine has been reported. We have summarized the most appropriate dosing regimens of posaconazole, fosravuconazole, voriconazole, and oteseconazole (VT-1161) to treat onychomycosis and superficial fungal infections. A structured search on PubMed and Google Scholar was conducted. Additionally, the bibliographies of selected articles were searched to identify relevant records. The number of records identified from the searches was 463, with 50 articles meeting the inclusion criteria for review. None of the new azoles are US FDA approved for onychomycosis treatment; however, an increasing number of studies have evaluated these agents. The efficacies (complete cure and mycologic cure) of the antifungal agents for dermatophyte great toenail onychomycosis treatment are terbinafine 250 mg/day × 12 weeks (Phase III trial) (38%, 70%), itraconazole 200 mg/day × 12 weeks (Phase III trial) (14%, 54%), posaconazole 200 mg/day × 24 weeks (Phase IIB) (54.1%, 70.3%), fosravuconazole 100 mg/day ravuconazole equivalent × 12 weeks (Phase III) (59.4%, 82.0%), and oteseconazole 300 mg/day loading dose × 2 weeks (Phase II), followed by 300 mg/week × 10 weeks (maintenance dose) (45%, 70%). Guidelines for monitoring are also presented.

Comparação da ação entre o antifúngico fluconazol e o óleo essencial de Melaleuca Alternifolia sobre amostras de leveduras do gênero Candida / Comparison of the action between the antifungal fluconazole and the essential oil of Melaleuca Alternifolia on samples of yeasts of the genus Candida

As onicomicoses são doenças causadas por fungos que acometem a pele, unhas e pelos, existindo diferentes formas clínicas e ocasionado por diversos agentes etiológicos. Os agentes causadores mais frequentes das onicomicoses são classificados como dermatófitos, não dermatófitos e leveduras. Dentre as leveduras destaca-se os fungos do gênero Candida, caracterizada como leveduriforme, em condições normais se apresentam como colonizantes, comensais e são consideradas oportunistas. A Candida albicans é a levedura mais comum de ser encontrada e está possui relatos de resistência ao fluconazol. A presença desta resistência representa um grande desafio terapêutico, pela escassez de alternativas no tratamento. Por conta disso muitas pessoas acabam optando por métodos alternativos para o controle deste tipo de infecção, um exemplo seria a aplicação de óleos essenciais naturais puros com ação combatente de microrganismos. O óleo essencial de Melaleuca, teve atividade antifúngica relatada por vários estudos usando diversas combinações de compostos originados da planta, mas sua aplicação mais comum é do óleo puro diluído. Porém os estudos aprofundando do quanto este composto possui de ação bactericida e antifúngica, comparados a medicamentos sintéticos, são escassos, mas sabe-se que com o uso frequente e correto do óleo ocasiona uma ação satisfatória. Objetivo geral foi descrever o efeito do óleo de Melaleuca sobre amostras de Candida albicans (ATT 90028) e Candida krusei (ATT 6258) comparando ao uso de Fluconazol.Método: Foi desenvolvida uma pesquisa qualitativa de caráter exploratório do uso tópico do óleo de Melaluca sobre Candida albicans (ATT 90028) e Candida krusei (ATT 6258) comparando com o antifúngico Fluconazol em método de difusão de disco.Os halos formados nos testes foram positivos para o Fluconazol, já para o óleo essencial de Melaleuca não constatando que a comparação por igual não é válida.

Onychomycosis are diseases caused by fungi that affect the skin, nails and hair, with different clinical forms and caused by different etiological agents. The most frequent causative agents of onychomycosis are classified as dermatophytes, non-dermatophytes and yeasts. Among the yeasts, the fungi of the genus Candida stand out, characterized as yeast, under normal conditions they present themselves as colonizers, commensals and are considered opportunistic. Candida albicans is the most common yeast to be found and has been reported to be resistant to fluconazole. The presence of this resistance represents a major therapeutic challenge, due to the scarcity of alternatives in the treatment. Because of this, many people end up opting for alternative methods to control this type of infection, an example would be the application of pure natural essential oils with microorganism-fighting action. Melaleuca essential oil has had antifungal activity reported by several studies using various combinations of compounds originating from the plant, but its most common application is as a diluted pure oil. However, the in-depth studies of how much this compound has bactericidal and antifungal action, compared to synthetic drugs, are scarce, but it is known that with the frequent and correct use of the oil it causes a satisfactory action. General objective was to describe the effect of Melaleuca oil on samples of Candida albicans (ATT 90028) and Candida krusei (ATT 6258) comparing to the use of Fluconazole. Method: A qualitative exploratory research was carried out on the topical use of Melaluca oil on Candida albicans (ATT 90028) and Candida krusei (ATT 6258) comparing it with the antifungal Fluconazole in a disc diffusion method. The halos formed in the tests were positive for Fluconazole, as for the essential oil of Melaleuca, not finding that the comparison is not valid.

Evaluation of cellulose based films comprising tea tree oil against dermatophytes and yeasts.

BACKGROUND: Onychomycosis is defined as infection caused by nondermatophytic molds and yeasts: tinea unguium is caused by dermatophytes. PURPOSE: Within this study, hydroxyethyl cellulose (HEC) as an important non-ionic, water-soluble cellulose derivative was chosen to develop formulations containing tea tree oil as active antifungal agent were developed and evaluated for their potential in the treatment of onychomycosis. METHODS: Two polymeric films based on HEC (HEC-B-04 and HEC-E-10) were obtained by solvent evaporation method and characterized in terms of appearance, disintegration, stickiness, elongation, rheological behavior and adhesiveness. Moreover, different strains of dermatophytes such as Trichophyton rubrum and yeasts as Candida albicans were treated with polymeric films containing tea tree oil (0.5 - 2 % v/v) in order to determine their antifungal potential by the inhibition zone assay. RESULTS: HEC-B-04 and HEC-E-10 were investigated by SEM measurements resulting in confluent surface morphology. HEC-B-04 and HEC-E-10 showed disintegration after 32.7 min and 34.0 min, respectively. Furthermore, HEC-E-10 revealed a moisture index of 1.74 and underpinned adhesive properties in terms of required detachment force with 4.86 N. HEC-E-10 pointed to the most antifungal one among the others against Trichophyton rubrum and Candida albicans. CONCLUSION: Taking these findings in consideration, promising adhesive onychial formulations were developed as forthcoming approach in treatment of nail infections.

Solubilization in vitro of tea tree oil and first results of antifungal effect in onychomycosis.

INTRODUCTION: Onychomycosis is the main cause of nail alteration. Hepatotoxicity, interference and low adherence to pharmacological treatment are associated. Therefore, our objective was to assess the in vitro effectiveness of tea tree essential oil (less harmful) against main causative agents of these infections. MATERIAL AND METHODS: Thrichophyton rubrum and Thrichophyton mentagrophytes were isolated and inoculated at a concentration of 3 × 105 CFU/mL in potato agar dextrose and tea tree essential oil at different concentrations to assess its effect by counting colony forming units and radial growth. RESULTS: Trichophyton rubrum growth inhibition was obtained at concentrations higher than 0.04% of the essential tea tree oil (p = 0.004). In the case of Thrichophyton mentagrophytes, inhibition was obtained at 0.02% (p = 0.017), and even complete inhibition at a final concentration of the oil at 0.07%. CONCLUSIONS: Tea tree essential oil inhibits the in vitro growth of the fungus and may be a less harmful alternative to the onychomycosis treatment.

A Review on Antifungal Efficiency of Plant Extracts Entrenched Polysaccharide-Based Nanohydrogels.

Human skin acts as a physical barrier; however, sometimes the skin gets infected by fungi, which becomes more severe if the infection occurs on the third layer of the skin. Azole derivative-based antifungal creams, liquids, or sprays are available to treat fungal infections; however, these formulations show various side effects on the application site. Over the past few years, herbal extracts and various essential oils have shown effective antifungal activity. Additionally, autoxidation and epimerization are significant problems with the direct use of herbal extracts. Hence, to overcome these obstacles, polysaccharide-based nanohydrogels embedded with natural plant extracts and oils have become the primary choice of pharmaceutical scientists. These gels protect plant-based bioactive compounds and are effective delivery agents because they release multiple bioactive compounds in the targeted area. Nanohydrogels can be applied to infected areas, and due to their contagious nature and penetration power, they get directly absorbed through the skin, quickly reaching the skin's third layer and effectively reducing the fungal infection. In this review, we explain various skin fungal infections, possible treatments, and the effective utilization of plant extract and oil-embedded polysaccharide-based nanohydrogels.

Combined laser and ozone therapy for onychomycosis in an in vitro and ex vivo model.

In order to develop a fast combined method for onychomycosis treatment using an in vitro and an ex vivo models, a combination of two dual-diode lasers at 405 nm and 639 nm wavelengths, in a continuous manner, together with different ozone concentrations (until 80 ppm), was used for performing the experiments on fungal strains growing on PDA agar medium or on pig's hooves samples. In the in vitro model experiments, with 30 min combined treatment, all species are inhibited at 40 ppm ozone concentration, except S. brevicaulis, which didn't show an inhibition in comparison with only ozone treatment. In the ex vivo model experiments, with the same duration and ozone concentration, A. chrysogenum and E. floccosum showed total inhibition; T. mentagrophytes and T. rubrum showed a 75% growth inhibition; M. canis showed a delay in sporulation; and S. brevicaulis and A. terreus did not show growth inhibition. This combined laser and ozone treatment may be developed as a fast therapy for human onychomycosis, as a potential alternative to the use of antifungal drugs with potential side effects and long duration treatments.

Onychoscopy: a quick and effective tool for diagnosing onychomycosis in a resource-poor setting.

INTRODUCTION: Onychomycosis is the most prevalent nail disease. Although clinical diagnosis of onychomycosis is easy, fungal culture as a confirmatory test requires an equipped laboratory and is time-consuming. Onychoscopy is a simple, quick, and inexpensive technique and may help clinicians increase the diagnostic accuracy of onychomycosis. The aim of this study was to identify common onychoscopic patterns of onychomycosis and correlate them with clinical subtypes of onychomycosis. METHODS: This study was performed in the dermatology outpatient department of a tertiary care hospital in northern India for 6 months. Clinically diagnosed cases of onychomycosis were confirmed by potassium hydroxide (KOH) mount. After obtaining informed written consent, these patients underwent onychoscopy with DermLite II hybrid m, 3Gen, polarized mode, 10× magnification. The common onychoscopic patterns were recorded and the data analyzed. RESULTS: The study included 60 confirmed cases of onychomycosis. The common onychoscopic patterns observed were jagged edges with spikes of the onycholytic area in 65.5% of cases, longitudinal striae in 77.6%, distal irregular termination or a "ruin pattern" in 82.7%, and chromonychia in 62.1%. Clinical types of onychomycosis showed a statistically significant association with chromonychia (p = 0.000), jagged edges with spikes (p = 0.015), and distal irregular termination (p = 0.016). CONCLUSIONS: Onychoscopy can be a complementary tool in clinical diagnosis of onychomycosis to alleviate the need for direct microscopy and culture.

Validation of a lateral flow immunochromatographic assay for tinea unguium diagnosis.

Tinea unguium is a common nail disease caused by dermatophytes. Although direct potassium hydroxide (KOH) microscopy and fungal culture are considered the gold standard for diagnosing this disease, their accuracy is insufficient. A lateral flow immunochromatographic assay (LFIA) kit, using a monoclonal antibody against Trichophyton rubrum, was developed and its sensitivity was recently improved 50% in vitro relative to its earlier version. The present study aimed to validate the clinical utility of this improved LFIA kit for diagnosing tinea unguium in comparison with direct KOH microscopy. A similar trial was simultaneously performed using scale samples from patients with tinea pedis to determine the assay's diagnostic potential. Nail samples, approximately 2 mg in weight, were collected from 112 non-treated tinea unguium patients and 56 non-tinea unguium patients. Samples from 25 tinea pedis patients and 20 non-tinea pedis patients were also collected. The sensitivity and specificity of the LFIA kit for tinea unguium was 84.8% (95/112) (95% confidence interval [CI], 76.8-90.9) and 83.9% (47/56) (95% CI, 71.7-92.4), respectively. The inconsistency rate was 15.5% (26/168) (95% CI, 10.4-21.9). The sensitivity and specificity of the LFIA kit for tinea pedis was 84.0% (21/25) and 100.0% (20/20), respectively. These results suggest that for diagnosing tinea unguium, the LFIA kit is a useful supplement to, but not a replacement for, direct KOH microscopy. For definitive diagnosis of suspected cases, appropriate sampling, repeated examinations, and a combination of diagnostic techniques are essential.