In Silico Drug Screening Based Development of Novel Formulations for Onychomycosis Management

Onychomycosis is a prominent fungal infection that causes discoloration, thickening, and mutilation leading to the separation of the nail from the nail bed. Treatment modalities for onychomycosis may include oral, topical, or combination therapy with antifungals and at times may require chemical or surgical intervention. The burden of side effects of antifungals is enormous, and therefore using molecular docking-based drug selection in context with the target keratin protein would ensure better disease management. Ciclopirox, Amorolfine HCl, Efinaconazole, Tioconazole, and Tavaborole were submitted for assessment, revealing that Amorolfine HCl is the best fit. Consequently, two formulations (Nail lacquer and nanoemulgel) were developed from Amorolfine HCl to validate the in silico screening outcomes. The formulations were further fortified with over-the-counter ingredients vis-a-vis with vitamin E in nail lacquer and undecylenic acid in nanoemulgel for their prominent roles in improving nail health. Both the formulations were systematically designed, optimized, and characterized. Amorolfine HCl containing nanoemulgel (NEG) was developed using undecylenic acid as an oil phase and thioglycolic acid as a penetration enhancer. The quality parameters evaluated were particle size, the zeta potential for nanoemulsion (NE) (78.04 ± 4.724 nm and −0.7mV, respectively), in vitro cumulative drug release (96.74% for NE and 88.54% for NEG), and transungual permeation (about 73.49% for NEG and 54.81% for NE). Nail lacquer was evaluated for the drying time, non-volatile content, and blush test. In vitro cumulative drug release of the developed nail lacquer and comparator marketed formulations were around 81.5% and 75%, respectively. Similarly, the transungual drug permeation was 6.32 μg/cm2 and 5.89 μg/cm2, respectively, in 24 h. The in silico guided preparation of both formulations containing Amorolfine HCl and over the counter ingredients is amenable for therapeutic use against onychomycosis and will be evaluated in the in vivo model.

Total Dystrophic Onychomycosis Successfully Treated with Efinaconazole Topical Solution in Times of COVID: A Case Study

Toenail onychomycosis is a common condition that is equally challenging for podiatrists and patients. This case study documents a 26-year-old woman with bilateral total dystrophic onychomycosis of at least 5 years' duration. She had previously failed to respond to treatment with ciclopirox nail lacquer 8% and despite hiding her condition with nail polish, was suffering from embarrassment, distress and low self-esteem. At initial consult, one hundred percent of both great toenails were affected. After discussion of all treatment options, the patient opted for topical efinaconazole 10% solution, once daily for 48 weeks. Significant improvement was noted at the first (4 week) assessment period. This improvement was maintained through each subsequent virtual consult and complete cure was seen at a 30-week follow-up visit. To the author's knowledge this is the first published report on the use of efinaconazole in total dystrophic onychomycosis. It suggests that the product may be effective in patients with even the most severe and treatment recalcitrant disease, who are unwilling or unable to tolerate systemic antifungal therapy.

COMPARATIVE STUDY OF EFFICACY OF ORAL TERBINAFINE ALONE AND ORAL TERBINAFINE WITH TOPICAL 8% CICLOPIROX OLAMINE IN ONYCHOMYCOSIS

Onychomycosis is a common fungal infection of nail plate caused by dermatophytes, non dermatophyte molds & yeasts. Tinea unguium on the other hand refers specifically to infection caused by dermatophytes. Onychomycosis represents 50% of all nail disorders and 30% of all mycotic infections of skin.1 It is distributed worldwide with prevalence of 3% to 9%. It is generally considered as a disease of middle aged and elderly affecting a large and significant number of people. There has been a recent increase in the incidence as well as a spectrum of causative pathogens associated with onychomycosis. 50 patients of onychomycosis who attended our outpatient department were randomly selected. These 50 patients were equally divided into two groups A and B. Patients in group A (25) were given only oral terbinafine 250mg/once daily for 12 weeks. Patients in group B (25) were given oral terbinafine 250mg/once daily for 12 weeks along with 8% Ciclopirox Olamine nail lacquer which is applied topically once daily at night. In our present study combination therapy give high mycological cure rates than oral terbinafine monotherapy. Combination therapy (oral terbinafine 250mg daily dose with 8% ciclopirox olamine nail lacquer) showed 70 % clinical cure rate and 60 % mycological cure.

TECHNOLOGICAL METHODS USED IN THE PRODUCTION OF THE DOSAGE FORM "NAIL LACQUER"

Therapy of nail disease is determined by the type of disease. We do not even think about how vulnerable and susceptible to various diseases our nails are. A number of diseases involve the use of local medicines. One of the dosage forms intended for topical use are medicinal lacquers. This article is devoted to the consideration and evaluation of the functional characteristics of excipients in the technology of medicinal lacquers.

Polishing the Therapy of Onychomycosis Induced by Candida spp.: Amphotericin B–Loaded Nail Lacquer

Onychomycosis induced by Candida spp. has several limitations regarding its treatment. Nail lacquers display the potential to overcome these drawbacks by providing therapeutic compliance and increasing local drug bioavailability. Thus, this work aimed to produce a nail lacquer loaded with Amphotericin B (AmB) and evaluate its performance. The AmB-loaded nail lacquer was produced and preliminarily characterized. An AmB quantification method was developed. Stability, drug release, permeability and anti-Candida activity assays were conducted. The analytical method validation met the acceptance criteria. The drug loading efficiency was 100% (0.02 mg/g of total product), whereas the AmB stability was limited to ≅ 7 days (≅ 90% remaining). The nail lacquer displayed a drying time of 187 s, non-volatile content of around 20%w/w, water-resistance of approximately 2%w/w of weight loss and satisfactory in vitro adhesion. Moreover, the in vitro antifungal activity against different Candida spp. strains was confirmed. The AmB release and the ex vivo permeability studies revealed that AmB leaves the lacquer and permeates the nail matrix in 47.76 ± 0.07% over 24 h. In conclusion, AmB-loaded nail lacquer shows itself as a promising extemporaneous dosage form with remarkable anti-Candida activity related to onychomycosis.

Ex vivo potential of a quinoline-derivative nail lacquer as a new alternative for dermatophytic onychomycosis treatment

Introduction. Onychomycosis infections currently show a significant increase, affecting about 10 % of the world population. Trichophyton rubrum is the main agent responsible for about 80 % of the reported infections. The clinical cure for onychomycosis is extremely difficult and effective new antifungal therapy is needed. Hypothesis/Gap Statement. Ex vivo onychomycosis models using porcine hooves can be an excellent alternative for evaluating the efficacy of new anti-dermatophytic agents in a nail lacquer. Aim. Evaluation of the effectiveness of a nail lacquer containing a quinoline derivative on an ex vivo onychomycosis model using porcine hooves, as well as the proposal of a plausible antifungal mechanism of this derivative against dermatophytic strains. Methodology. The action mechanism of a quinoline derivative was evaluated through the sorbitol protection assay, exogenous ergosterol binding, and the determination of the dose-response curves by time-kill assay. Scanning electron microscopy evaluated the effect of the derivative in the fungal cells. The efficacy of a quinoline-derivative nail lacquer on an ex vivo onychomycosis model using porcine hooves was evaluated as well. Results. The quinoline derivative showed a time-dependent fungicidal effect, demonstrating reduction and damage in the morphology of dermatophytic hyphae. In addition, the ex vivo onychomycosis model was effective in the establishment of infection by T. rubrum. Conclusion. Treatment with the quinoline-derivative lacquer showed a significant inhibitory effect on T. rubrum strain in this infection model. Finally, the compound presents high potential for application in a formulation such as nail lacquer as a possible treatment for dermatophytic onychomycosis.

The rheologically-complex fluid beauty of nail lacquer formulations

We focus on conceptual and experimental challenges underlying the rheological characterization of commercial nail lacquer formulations, and the fluid mechanics quests relevant to the problem of painting nails or getting them painted.