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Background: Glomus tumors are uncommon tumors and their occurrence in the foot is even less common. Glomus tumors of the toes are often missed, causing delays in diagnosis and treatment. We report an ambispective observational study of glomus tumors of the toes that were treated at our institution. Methods: We reviewed the records of all the patients who underwent excision of toe glomus tumors in our department from January 2010 to September 2022. The follow-up data were collected from the outpatient records and by telephonic interview. Single Assessment Numeric Evaluation (SANE) score, Foot and Ankle Outcome Score (FAOS), and the Foot Function Index (FFI) were collected. Results: Out of all the patients treated for glomus tumors, we found that 7 patients had glomus tumors of the toes. Of the 7 patients, 6 were women and 1 was a male. The mean follow-up of our patients was 66.4 months (range, 7-109 months). Of the 7 patients, 1 presented with recurrent glomus tumor 30 months following the primary operation, for which she underwent excision again, after which she was symptom free. Another patient who developed recurrent symptoms on telephonic interview refused any further treatment. Among the 6 patients who were symptom-free at follow-up (including the patient who underwent excision for the recurrent tumor), the median SANE score, and FFI were 99.5 (IQR, 96-100) and 0.5 (IQR, 0-2) respectively. The mean FAOS was 96 (SD, 3.3). Conclusion: Surgical excision of the subungual toe glomus tumors can be curative. Recurrence of toe glomus tumors was noted in 2 patients (29%), one of whom refused further surgery. Re-excision in the other patient resulted in complete resolution of symptoms. Level of Evidence: Level III, ambispective observational study. [ABSTRACT FROM AUTHOR]

The humanoid nail is considered an exceptional protective barrier that is formed mainly from keratin. Onychomycosis is the cause of 50% of nail infections that is generally caused by dermatophytes. Firstly, the infection was regarded as a cosmetic problem but because of the tenacious nature of onychomycosis and its relapses, these infections have attracted medical attention. The first line of therapy was the oral antifungal agents which were proven to be effective; nevertheless, they exhibited hepato-toxic side effects, alongside drug interactions. Following, the opportunity was shifted to the topical remedies, as onychomycosis is rather superficial, yet this route is hindered by the keratinized layers in the nail plate. A potential alternative to overcome the obstacle was applying different mechanical, physical, and chemical methods to boost the penetration of drugs through the nail plate. Unfortunately, these methods might be expensive, require an expert to be completed, or even be followed by pain or more serious side effects. Furthermore, topical formulations such as nail lacquers and patches do not provide enough sustaining effects. Recently, newer therapies such as nanovesicles, nanoparticles, and nanoemulsions have emerged for the treatment of onychomycosis that provided effective treatment with possibly no side effects. This review states the treatment strategies such as mechanical, physical, and chemical methods, and highlights various innovative dosage forms and nanosystems developed in the last 10 years with a focus on advanced findings regarding formulation systems. Furthermore, it demonstrates the natural bioactives and their formulation as nanosystems, and the most relevant clinical outcomes. [ABSTRACT FROM AUTHOR]

The efficacy of topical antifungal therapy in onychomycosis has been hindered by the failure of the antimycotic to permeate the nail plate. This research aims to design and develop a transungual system for the effective delivery of efinaconazole utilizing constant voltage iontophoresis. Seven prototype drug-loaded hydrogel formulations (E1–E7) were prepared to assess the influence of solvent (ethanol) and cosolvent (Labrasol®) on transungual delivery. Optimization was performed to evaluate the effect of three independent variables; voltage, solvent-to-cosolvent ratio, and penetration enhancer (PEG 400) concentration on critical quality attributes (CQAs), such as drug permeation and loading into the nail. The selected hydrogel product was characterized for pharmaceutical properties, efinaconazole release from the nail, and antifungal activity. Preliminary data indicates ethanol, Labrasol®, and voltage influence the transungual delivery of efinaconazole. Optimization design indicates a significant impact by applied voltage (p-0.0001) and enhancer concentration (p-0.0004) on the CQAs. Excellent correlation between selected independent variables and CQAs was confirmed by the high desirability value (0.9427). A significant (p < 0.0001) enhancement in the permeation (~78.59 µg/cm2) and drug loading (3.24 µg/mg) was noticed in the optimized transungual delivery with 10.5 V. FTIR spectral data indicates no interaction between the drug and excipients, while the DSC thermograms confirmed the amorphous state of the drug in the formulation. Iontophoresis produces a drug depot in the nail that releases above the minimum inhibitory concentration level for an extended period, potentially reducing the need for frequent topical treatment. Antifungal studies further substantiate the release data and have shown remarkable inhibition of Trichophyton mentagrophyte. Overall, the promising results obtained here demonstrate the prospective of this non-invasive method for the effective transungual delivery of efinaconazole, which could improve the treatment of onychomycosis. [ABSTRACT FROM AUTHOR]

Background: Onychomycosis, the most prevailing affliction of the nail, accounts for approximately 90% of the toenail infection worldwide. Owing to this infection, the affected patients experience reduced quality of their life as its awful appearance undermines their daily activities and social interactions. Onychomycosis is notoriously strenuous to cure. Systemic therapy, though effective, possess severe complication of toxicities, contra‐indication, and drug–drug interaction. Albeit topical therapy is favorable to its localized effect, its potency relates to the effective concentration of the antifungal drugs achieved at the infection site. An approach to accomplish this goal would be acquiring benefits from the terpenes as penetration enhancers from natural sources. This investigation aimed to study the effectiveness of six terpenes, namely safranal, lavandulol, rose oxide, 3‐methyl‐2‐butene‐1‐ol, linalool, and limonene, as potential penetration enhancers for improved nail permeation of fluconazole through the human nail. Methods: Ex vivo permeation experiments were carried out by soaking the nail clippings of human volunteers in control and working solutions containing fluconazole (5 mg/ml) per se and fluconazole (5 mg/ml) with 6% of each terpene, including safranal, lavandulol, rose oxide, 3‐methyl‐2‐butene‐1‐ol, linalool, and limonene, respectively, for 48 h. The amount of fluconazole in nail clippings was quantified using an HPLC method. Results: Statistical analysis showed that fluconazole transungual permeation was influenced by the studied terpenes in the following order: safranal >lavandulol acetate >limonene > rose oxide (p‐value >0.05) while the other terpenes showed no significant difference with the control group and safranal represents as the most effective permeation enhancer for the transungual delivery of fluconazole. Conclusion: It is concluded that the safranal can be successfully used as a safe and potential permeation enhancer to enhance the transungual delivery of fluconazole for the treatment of onychomycosis. [ABSTRACT FROM AUTHOR]

Introduction: Onychomycosis is a fungal disorder of the nail which afflicts 5% of the population worldwide. The disease is strenuous to cure as it is chronic, hard to eliminate and tends to recur. Topical therapy is at the forefront for the treatment of many disorders of nail. However, the success rate of topical therapy has been halted owing to the poor permeation of topical therapeutics across densely keratinized nail barrier. Therefore, ungual drug permeation must be improved for an effective topical therapy. An approach to achieve this goal would be the use of terpenes from natural sources as potential penetration enhancers. This study is aimed to explore the effectiveness of some novel terpenes as potential penetration enhancers on transungual delivery of terbinafine. Methods: Ex-vivo permeation studies were performed by sopping the nail clippings of healthy human volunteers in control and working solutions containing terbinafine (5mg/ml) per se and terbinafine (5mg/ml) with 6% of each terpenes including lavandulol, safranal, rose oxide, limonene, 3-methyl-2-butene-1-ol, and linalool respectively for 48 hours. The terbinafine concentration in nail samples was determined using a HPLC method. Results: Statistical analysis showed that studied terpenes increase transungual penetration of terbinafine in the following order: linalool > rose oxide > 3-methyl-2-butene-1-ol > safranal> limonene>lavandulol acetate. Accordingly, linalool was found to be the most effective penetration enhancer for the transungual delivery of terbinafine. Conclusion: It is concluded that linalool can be used as safe and potential penetration enhancer for enhancing the transungual delivery of terbinafine for onychomycosis.

As regulatory and technical landscapes for pharmaceutical formulation development are rapidly evolving, a risk-management approach using multivariate analysis is highly essential for designing a product with requisite critical quality attributes (CQA). Efinaconazole, a newly approved poorly water-soluble antifungal triazole drug has poor permeability. Spanlastics, new-generation surfactant nanovesicles, being fluidic, help improve the permeability of drugs. Therefore, we optimized efinaconazole spanlastics using the concepts of Formulation-by-Design (FbD) and explored the feasibility of transungual delivery for the management of onychomycosis. Using the Ishikawa fishbone diagram, the risk factors that may have an impact on the CQA of efinaconazole spanlastic vesicles were identified. Application of the Plackett–Burman experimental design facilitated the screening of eight different formulation and process parameters influencing particle size, transmittance, relative deformability, zeta potential, entrapment efficiency, and dissolution efficiency. With the help of Pareto charts, the three most significant factors were identified, viz., vesicle builder (Span), edge activator (Tween), and mixing time. The levels of these three critical variables were optimized by FbD to reduce the particle size and maximize the transparency, relative deformability, encapsulation efficiency, and dissolution efficiency of efinaconazole spanlastic nanovesicles. Bayesian and Lenth's analysis and mathematical modeling of the experimental data helped to quantify the critical formulation attributes required for getting the formulation with optimum quality features. The optimized efinaconazole-loaded spanlastic vesicles had a particle size of 197 nm, transparency of 91%, relative deformability of 12.5 min, and dissolution efficiency of 81.23%. The spanlastic formulation was incorporated into a gel and explored ex vivo for transungual delivery. This explorative study provides an example of the application of principles of risk management, statistical multivariate analysis, and the FbD approach in developing efinaconazole spanlastic nanovesicles. [ABSTRACT FROM AUTHOR]

The efficacy of topical antifungal therapy in onychomycosis has been hindered by the failure of the antimycotic to permeate the nail plate. This research aims to design and develop a transungual system for the effective delivery of efinaconazole utilizing constant voltage iontophoresis. Seven prototype drug-loaded hydrogel formulations (E1–E7) were prepared to assess the influence of solvent (ethanol) and cosolvent (Labrasol®) on transungual delivery. Optimization was performed to evaluate the effect of three independent variables; voltage, solvent-to-cosolvent ratio, and penetration enhancer (PEG 400) concentration on critical quality attributes (CQAs), such as drug permeation and loading into the nail. The selected hydrogel product was characterized for pharmaceutical properties, efinaconazole release from the nail, and antifungal activity. Preliminary data indicates ethanol, Labrasol®, and voltage influence the transungual delivery of efinaconazole. Optimization design indicates a significant impact by applied voltage (p-0.0001) and enhancer concentration (p-0.0004) on the CQAs. Excellent correlation between selected independent variables and CQAs was confirmed by the high desirability value (0.9427). A significant (p < 0.0001) enhancement in the permeation (~78.59 µg/cm2) and drug loading (3.24 µg/mg) was noticed in the optimized transungual delivery with 10.5 V. FTIR spectral data indicates no interaction between the drug and excipients, while the DSC thermograms confirmed the amorphous state of the drug in the formulation. Iontophoresis produces a drug depot in the nail that releases above the minimum inhibitory concentration level for an extended period, potentially reducing the need for frequent topical treatment. Antifungal studies further substantiate the release data and have shown remarkable inhibition of Trichophyton mentagrophyte. Overall, the promising results obtained here demonstrate the prospective of this non-invasive method for the effective transungual delivery of efinaconazole, which could improve the treatment of onychomycosis.

Glomus tumors are rare soft-tissue neoplasms that constitute 2% of all soft-tissue tumors in the extremities. They are painful lesions that can impair quality of life. Diagnosis is often delayed as they can easily be confused with more common pathologies. They are best diagnosed through MRI scan or ultrasonography of the concerned digit. We present two cases in this article, one of a subungual glomus tumor of the great toe (Hallux) and one of the index finger. Both tumors had a delay in diagnosis as this tumor cannot easily be diagnosed through simple radiographs. They showed classical clinical symptoms. Both were eventually diagnosed on MRI scan. Surgical excision is the gold standard in treatment of subungual glomus tumors and is also curative. We used a transungual approach for the hallux and a lateral subperiosteal approach for the index finger. In conclusion, glomus tumors are rare, benign tumors that commonly occur in the sub-ungual region. High clinical suspicion is important for clinical diagnosis. MRI scan and ultrasound can diagnose the tumor and yield information about local spread. Surgical excision is usually curative with approximately 10% chance of recurrence and rare chance of malignant transformation. [ABSTRACT FROM AUTHOR]

Microneedles (MNs) are micron-scaled needles measuring 100 to 1000 μm that were initially explored for delivery of therapeutic agents across the skin. Considering the success in transcutaneous drug delivery, the application of microneedles has been extended to different tissues and organs. The review captures the application of microneedles to the oral mucosa, the eye, vagina, gastric mucosa, nail, scalp, and vascular tissues for delivery of vaccines, biologics, drugs, and diagnostic agents. The technology has created easy access to the poorly accessible segments of eye to facilitate delivery of monoclonal antibodies and therapeutic agents in management of neovascular disease. Microporation has been reported to drastically improve the drug delivery through the poorly permeable nail plate. Curved microneedles and spatially designed microneedle cuffs have been found to be capable of delivering stem cells and therapeutic macromolecules directly to the cardiac tissue and the vascular smooth muscle cells, respectively. Besides being minimally invasive and patient compliant, the technology has the potential to offer viable solutions to deliver drugs through impermeable barriers owing to the ability to penetrate several biological barriers. The technology has been successful to overcome the delivery hurdles and enable direct delivery of drug to the target sites, thus maximizing the efficacy thereby reducing the required dose. This review is an attempt to capture the non-dermatological applications of microneedles being explored and provides an insight on the future trends in the field of microneedle technology. Pictorial representation of different microneedle application. [ABSTRACT FROM AUTHOR]

Onychomycosis is a common fungal infection of the nails that mostly affects the elderly and athletes. Antifungal drug-like itraconazole is one of the therapeutic agents of choice for the topical treatment of onychomycosis. The current work aimed for the preparation and optimization of itraconazole-loaded nail lacquer formulation. Central composite design was employed; independent variables were polymer concentration (X1) and thioglycolic acid (TGA) concentration (X2). While the dependent variables were cumulative amount of drug permeated per unit area (CADP/A, Y1), drying time (Y2) and nonvolatile content (Y3). The optimized formulation was characterized for various parameters including ex-vivo permeation study, confocal laser scanning microscopy (CLSM) and antifungal study. The optimized nail lacquer formulation (F7) exhibited CADP/A of 198.23 µg/cm2, drying time of 185 s and nonvolatile content of 97.23%. The scanning electron microscopy of goat hoof treated with optimized nail lacquer formulation demonstrated loosening of the structure and marked increase in surface roughness. The CLSM micrograph of goat hoof treated with optimized nail lacquer formulation demonstrated that the probe dye was eventually distributed and penetrated through the hoof. Bio-adhesiveness analysis showed that the prepared nail lacquer film has ample adhesiveness to be maintained on the nail plate surface for a sufficient time. In antifungal study, the optimized nail lacquer, and marketed gel exhibited a zone inhibition of 21 mm, and 10 mm against Candida albicans, respectively. The stability study showed that the optimized nail lacquer is stable at storage condition. The prepared nail lacquers have been shown to serve as a useful dosage form for the delivery of itraconazole across nail plate for controlling the problems associated with onychomycosis. [ABSTRACT FROM AUTHOR]

The nail unit is the largest cutaneous musculo-skeletal appendage. The management of nail disorders is an onerous task owing to the disease manifestations and anatomical structure of the nail plate. The topical treatment of nail infections/disorders has been a centerpiece of nail research in the past few decades as it offers a much safer and focused alternative to conventional oral therapy. However, transungual delivery had its challenges. This necessitated a lookout for novel approaches that enhanced treatment efficacy and reduced treatment time. Moreover, curing the nail condition using topical delivery has been challenging due to the lack of a validated animal model to determine the efficacy of the formulation and to establish a mathematical model that can help in predicting the desirable attributes of the formulation and permeation of various molecules through the nail plate. This review is based on publications retrieved by a selective search in PubMed. The purpose of this review is to provide an overview of nail anatomy and its disorders, factors affecting nail delivery, diagnostic procedures, current approaches, and promising approaches to treat nail infections/disorders including nail lacquers and the role of permeation enhancers, in-vitro models. This review also covers current available treatments and treatments under clinical trial. [ABSTRACT FROM AUTHOR]

As regulatory and technical landscapes for pharmaceutical formulation development are rapidly evolving, a risk-management approach using multivariate analysis is highly essential for designing a product with requisite critical quality attributes (CQA). Efinaconazole, a newly approved poorly water-soluble antifungal triazole drug has poor permeability. Spanlastics, new-generation surfactant nanovesicles, being fluidic, help improve the permeability of drugs. Therefore, we optimized efinaconazole spanlastics using the concepts of Formulation-by-Design (FbD) and explored the feasibility of transungual delivery for the management of onychomycosis. Using the Ishikawa fishbone diagram, the risk factors that may have an impact on the CQA of efinaconazole spanlastic vesicles were identified. Application of the Plackett–Burman experimental design facilitated the screening of eight different formulation and process parameters influencing particle size, transmittance, relative deformability, zeta potential, entrapment efficiency, and dissolution efficiency. With the help of Pareto charts, the three most significant factors were identified, viz., vesicle builder (Span), edge activator (Tween), and mixing time. The levels of these three critical variables were optimized by FbD to reduce the particle size and maximize the transparency, relative deformability, encapsulation efficiency, and dissolution efficiency of efinaconazole spanlastic nanovesicles. Bayesian and Lenth’s analysis and mathematical modeling of the experimental data helped to quantify the critical formulation attributes required for getting the formulation with optimum quality features. The optimized efinaconazole-loaded spanlastic vesicles had a particle size of 197 nm, transparency of 91%, relative deformability of 12.5 min, and dissolution efficiency of 81.23%. The spanlastic formulation was incorporated into a gel and explored ex vivo for transungual delivery. This explorative study provides an example of the application of principles of risk management, statistical multivariate analysis, and the FbD approach in developing efinaconazole spanlastic nanovesicles.

Transungual drug delivery system (TDDS) is basically the system which deals with the treatment of diseases like onychomycosis and nail psoriasis. The treatment involves the drug being delivered through the keratinized nail plate. The drug penetration is done basically into the nail plate because it is the main route for drug penetration. Various other formulations like gels and creams are available. This system is efficient in nails treatment. In these types of disorders, drugs are absorbed into the unit of nail and to the nail plate. Permeability of nail is low and however limits early-stage disease topical therapy in cases like onychomycosis which is fungal infection of nail. Current researches are based on nail permeation which suggests the alterations in the barriers of nail plate by chemical treatment and other methods like mechanical or penetration enhancers. Medicated form of lacquers shows maximum anti-fungal activity. Lacquers are the productive forms which treats disorders of nail that is concluded by current reviews. [ABSTRACT FROM AUTHOR]

The objective of the present study was to prepare valencene (sesquiterpene) containing invasomes for itraconazole (ITZ) transungual delivery using central composite design. The phospholipid (X1) and valencene (X2) were selected as an independent variables, while vesicles size (Y1), entrapment efficiency (Y2) and in vitro drug release (Y3) were chosen as dependent variables. The antifungal activity of optimized formulation was screened against Trichophyton rubrum, a common causative onychomycosis pathogen, by cup plate method. The optimized ITZ-loaded invasomes formulation presented vesicles size of 176.8 ± 6.03 nm, entrapment efficiency of 83.21 ± 4.11% and in vitro drug release of 75.22 ± 5.03%. The ITZ-loaded invasomes gel formulation showed good homogeneity, pH 6.5 ± 0.23, viscosity 7.33 ± 0.67 Pa s and drug content 94.13 ± 1.13%. The spreadability and extrudability of developed ITZ-loaded invasomes gel were found to be 7.85 ± 0.24 gcm/s and 162 ± 2.74 g, respectively. The ITZ-loaded invasomes gel presented 71.11 ± 3.65% cumulative permeation of drug via goat hooves. The in vitro antifungal activity depicted that the ITZ-loaded invasomes gel and marketed preparation were presented zone of inhibition of 21.42 mm and 10.64 mm against T. rubrum respectively. Hence the prepared ITZ-loaded invasomes formulation could therefore be a promising topical dosage to mitigate the indications and hasten the cure for onychomycosis than conventional available therapies. [ABSTRACT FROM AUTHOR]

Background: Onychomycosis, a fungal nail infection, is an important problem as it may cause local pain, paresthesia, difficulties in performing activities of daily life, and impair social interactions. Systemic treatment of onychomycosis presents safety issues due to possible drug‐drug interactions and severe side effects. Although topical therapy of onychomycosis is advantageous due to its localized effect, the efficacy of such therapy depends on achieving effective concentrations of antifungal agents at the infection site. An approach to reach to this end would be driving benefit from synergic activity of antifungal agents for example itraconazole and monoterpenes. However, because of low transungual penetration of itraconazole, a molecule with high molecular weight and very low water‐solubility, the effect of the latter compounds on itraconazole nail delivery should be investigated, which was the aim of this study. Methods: Ex vivo permeation experiments were carried out through soaking the nail clippings of ten healthy volunteers in control and working solutions containing itraconazole (1 mg mL−1) and itraconazole (1 mg mL−1) plus 6% of each monoterpene including camphor, eucalyptol, menthol, and thymol, respectively, for 36 hours. The amount of itraconazole in nail clippings was quantified hereafter using a validated HPLC method. Results: Statistical analysis showed that itraconazole transungual permeation was not influenced by the studied monoterpenes (P value >.05). Conclusion: These results provided a new perspective for designing topical dosage forms for the treatment of onychomycosis. [ABSTRACT FROM AUTHOR]

Objectives: An attempt was made to prepare transparent nail lacquer containing natural antifungal agent obtained from extract of whole plant of Cissus quadrangularis for the treatment of onychomycosis. Methods: The extract of C. quadrangularis was evaluated for antifungal study against Candida albicans. Minimum inhibitory concentration of extract against C. albicans was performed to get the amount of extract to be loaded in the nail lacquer. Extract was further evaluated for phytochemical study such as test for steroids, glycoside and flavonoids. Nail lacquer was prepared by using nitrocellulose, ethyl cellulose, ethyl acetate, salicylic acid, dibutyl phthalate, extract of C. quadrangularis and acetone with continuous stirring. The nail lacquer of fluconazole was prepared and compared with formulation. Formulations of nail lacquer were evaluated for drying time, gloss, nonvolatile content, water resistance, viscosity, smoothness of flow. In-vitro transungual permeation study was performed through goat nail. Results: Phytoconstituents such as flavonoid and quinine were found present in the extract. Antifungal activity of nail lacquer and fluconazole formulation against C. albicans was found good (zone of inhibition of 20±2mm at 50mg/ml, 16±1mm for 40mg/ml respectively). Drying time of formulation was 62-70 s with visually seen glossiness of formulation. Formulation of nail lacquer showed good non-volatile content, water resistance and viscosity with smoothness of flow. In-vitro permeation of F7 formulation showed 90.9% of permeation which was faster within 24 hr. Conclusion: Thus, C. quadrangularis extract loaded antifungal nail lacquer could be a good choice for treatment of onchomycosis rather than fluconazole. [ABSTRACT FROM AUTHOR]

Luliconazole-loaded microemulgels containing different permeation enhancers were formulated for transungual drug delivery for the management of onychomycosis, onychomycosis, which affects nails. The physicochemical properties like droplet size, zeta potential, pH, viscosity, spreadability, extrudability, oil binding capacity, drug content, and microscopic study were evaluated. The Pseudo-ternary phase diagram was constructed for the formulation of microemulsions (MEs) by keeping the K m ratio constant at 3:1 and characterized for clarity, mean droplet size, zeta potential, viscosity, pH, transmittance, refractive index, and stability. The ME mean droplet size and zeta potential were found in the range of 38.78 to 171.4 nm, and 0.00 to − 6.6 mV, respectively. Prepared MEs were converted into microemulgel by adding a 2.5% gelling agent (Carbapol 934) in the external phase, and a drug release study was conducted. Formulation E3 showed better drug release and was chosen as the control. Four different penetration enhancers were added separately within E3 and further evaluated for pH, viscosity, spreadability, extrudability, oil binding capacity, drug content, microscopic study, Compatibility study, XRD, and DSC. A favorable docking score was observed between luliconazole and Lanosterol 14-alpha-demethylase. In-vitro cumulative drug release at the end of 24 h from E3-SS, containing sodium sulfide as a penetration enhancer, was found to be 94.70% and was 2 times more than the control formulation. Ex-vivo transungual permeation studies through cutting nail clippings were found to be in the range of 28.18 - 36.52 µg/mm2. The microemulgels tagged as E3, E3-SS, and E3-SL showed a significant zone of inhibition against Candida albicans and Aspergillus fumigatus as compared to the marketed formulation. [Display omitted] • In-vitro drug release from E3-SS, at the end of 24 h was found to be 94.70%. • The solubility of Luliconazole in sesame oil was found to be 0.187 mg/ ml. • Prepared microemulgels showed good texture profile. • Microemulsions showed globule size ranges from 38.78 to 171.4 nm. [ABSTRACT FROM AUTHOR]

Onychomycosis constitutes the most common fungal infection of nail affecting finger and toe nails as well. Antifungals found to be effective in the treatment of onychomycosis. However, transport of oral antifungal agents exhibits more toxicity and requires longer treatment period. Medicated nail lacquers proved to cause lesser toxicity and required shorter treatment period. It provides not only finger/toe nail infection therapy and but also act as a protection for nails. Thus, the objective behind the present investigation was to develop nail lacquer for transungual delivery of tolnaftate. Its potency had been assessed by evaluating penetration efficiency across the bovine hoof membrane. Preliminary studies aided the optimization of thioglycolic acid as permeation enhancer (HEFmax 0.60 ± 0.377) and menthol as local anaesthetic. n-butanol:isopropyl alcohol with optimum drying time of 60 sec was selected as optimum solvent system. In total nine formulations were developed based on 32 full factorial design and characterized for drying time, non-volatile content, in vitro adhesion and permeation study. Based on highest desirability, F6 was selected as an optimized formulation and evaluated for viscosity, stability and antifungal activity. Optimized formulation exhibited optimum viscosity and stability for 1 month period. Better antifungal activity was observed against Candida albicans in comparison to the control formulation. Thus, it can be concluded from the investigation that nail lacquer could proved to be a better alternative for transungual delivery of tolnaftate.

This study was to search some natural penetration enhancer and formulate them in a transungual drug delivery formulation. This natural penetration enhancer helps to overcome the main problem in front of success of transungual drug delivery system. We selected to formulate fluconazole as a model drug for the nail fungal infection treatment with extracted penetration enhancer (PE). Model drug i.e. fluconazole was formulated with the natural extracted penetration enhancer with different deigned formula. The solvent for PE extraction was methanol and that extracts were air dried. The cadaver human nail plates were used for penetration study, were collected from the same volunteer for negligence in the thickness and chemical composition concentration in the nail plate. The extracted PE (pelargonium hortorum) was selected for formulation on the basis of ethanopharmaceutical history. The human cadaver nail plates were treated with the formulation with and without the extracted PEs. Ex - vivo drug penetration was evaluated by Franz diffusion cells using cadaver human nail plate upto 36 hours. The drug filmability was found to be best with the polymer like HPMC K4M, Ethyl cellulose and hydroxyl propyle cellulose in the ratio of 1:1:1, mixture of propanol and butanol in 7:3 as solvent and 30% w/w DBP as plasticizer. The formula FT25AP4 shows total 35.67% drug penetraion i.e. near about two times of drug penetration across the nail plate when compare to the same formulation but without any penetration enhancer. The “p” value (0.0011) of drug penetration was less than 0.05.

The present investigation focused on developing, optimizing, and evaluating a novel liposome-loaded nail lacquer formulation for increasing the transungual permeation flux of terbinafine HCl for efficient treatment of onychomycosis. A three-factor, three-level, Box-Behnken design was employed for optimizing process and formulation parameters of liposomal formulation. Liposomes were formulated by thin film hydration technique followed by sonication. Drug to lipid ratio, sonication amplitude, and sonication time were screened as independent variables while particle size, PDI, entrapment efficiency, and zeta potential were selected as quality attributes for liposomal formulation. Multiple regression analysis was employed to construct a second-order quadratic polynomial equation and contour plots. Design space (overlay plot) was generated to optimize a liposomal system, with software-suggested levels of independent variables that could be transformed to desired responses. The optimized liposome formulation was characterized and dispersed in nail lacquer which was further evaluated for different parameters. Results depicted that the optimized terbinafine HCl-loaded liposome formulation exhibited particle size of 182 nm, PDI of 0.175, zeta potential of −26.8 mV, and entrapment efficiency of 80%. Transungual permeability flux of terbinafine HCl through liposome-dispersed nail lacquer formulation was observed to be significantly higher in comparison to nail lacquer with a permeation enhancer. The developed formulation was also observed to be as efficient as pure drug dispersion in its antifungal activity. Thus, it was concluded that the developed formulation can serve as an efficient tool for enhancing the permeability of terbinafine HCl across human nail plate thereby improving its therapeutic efficiency. [ABSTRACT FROM AUTHOR]

Onychomycosis is a fungal infection of nails that is widespread and difficult to treat because of the impermeable nature of human nails. Topically applied anti-fungal agents cannot penetrate this structure, and treatment regimens often resort to systemic antifungals with concomitant side effects. One recent clinical study suggested that mechanical fenestration of the nail using an intelligent nail drill might be a possible solution to this problem. In this work, an in vitro model of the transungual delivery of antifungal agents is presented, which utilizes real nail tissue and an inline flow system. This system was deployed to measure transungual delivery of ciclopirox and determined that nail fenestration improved drug delivery by 3–4-fold after 42 days. This study bolsters the argument that nail fenestration should be accepted as a pretreatment for onychomycosis and offers a way of evaluating new drugs or formulations designed to combat this condition.

Context: The systemic treatment of onychomycosis has been hampered by the reported side effects of antifungals in addition to the limited blood circulation to the affected nails. Topical ungual treatment would circumvent the limitations of systemic onychomycosis treatment. Objective: Preparation and characterization of nail penetration enhancer containing nanovesicles (nPEVs) loaded with sertaconazole for topical treatment of onychomycosis. Materials and methods: nPEVs were prepared using different nail penetration enhancers (N-acetyl-L-cysteine, thioglycolic acid, thiourea and ethanol) by the thin film hydration method, and characterized for their particle size, zeta potential, entrapment efficiency (EE%), elasticity, viscosity, physical stability and morphology. The selected nPEVs formula and the marketed Dermofix® cream were compared in terms of nail hydration, transungual drug uptake and antifungal activity againstTrichophyton rubrum. Results: N-acetyl-l-cysteine was the optimum nail penetration enhancer for incorporation within vesicles. nPEVs showed high EE% of sertaconazole ranging from 77 to 95%, a size ranging from 38–538 nm and a zeta potential ranging from +48 to +72 mV. The selected nPEVs formula displayed spherical morphology and good storage stability. Compared to the conventional marketed cream, the selected nPEVs formula showed 1.4-folds higher hydration and drug uptake enhancement into nail clippings. Furthermore, it showed significantly higher zone of inhibition forTrichophyton rubrum(20.9 ± 0.25 mm) than the marketed cream (11.6 ± 0.44 mm). Conclusion: Nail penetration enhancer containing nanovesicles (nPEVs) present a very promising option, worthy of clinical experimentation on onychomycotic patients. [ABSTRACT FROM PUBLISHER]

Nail disorders are beyond cosmetic concern; besides discomfort in the performance of daily chores, they disturb patients psychologically and affect their quality of life. Fungal nail infection (onychomycosis) is the most prevalent nail-related disorder affecting a major population worldwide. Overcoming the impenetrable nail barrier is the toughest challenge for the development of efficacious topical ungual formulation. Sophisticated techniques such as iontophoresis and photodynamic therapy have been proven to improve transungual permeation. This article provides an updated and concise discussion regarding the conventional approach and upcoming novel approaches focused to alter the nail barrier. A comprehensive description regarding preformulation screening techniques for the identification of potential ungual enhancers is also described in this review while highlighting the current pitfalls for the development of ungual delivery. [ABSTRACT FROM AUTHOR]

The objective of the present study was to design and develop a microemulsion based transungual drug delivery formulation of ciclopirox olamine using colloidal carrier for treatment of onychomycosis. Capmul PG8 was selected as oil phase due to the high solubility of ciclopirox in it as compared to other oils and Cremophor EL and Transcutol P were used as surfactant and cosurfactant respectively. Pseudoternary phase diagrams were constructed using different ratio of Smix (surfactant:cosurfactant). The phase diagram obtained from 1:3 ratio showed largest microemulsion region. The construction of microemulsion was further optimized by D-optimal mixture design, taking oil, Smix and water as independent variables and globule size, transungual flux, and nail drug loading as response variables. Mathematical equations and response surface plots were used to correlate the dependent and independent variables. The optimized composition of microemulsion was predicted by numerical optimization technique on the basis of the highest desirability value. The predicted optimized microemulsion which contained 2% oil, 40% Smix, and 58% water was incorporated into Carbopol 940 gel base and evaluated for transungual drug permeation. The optimized microemulsion based gel formulation showed globule size (25.8±1.2 nm), transungual flux (0.436±0.014 μg/cm2/h), and drug loading in nail plate (82.89±5.74 μg) which was in close agreement with the predicted value of response variable by the optimization software, i.e. 26.145 mm, 0.431 μg/cm2/h, and 81.023 μg, respectively. These results confirmed that the D-optimal mixture design can be successfully employed for designing and development of microemulsion based formulation of ciclopirox olamine. [ABSTRACT FROM AUTHOR]

Synopsis Pre-clinical development comprises of different procedures that relate drug discovery in the laboratory for commencement of human clinical trials. Pre-clinical studies can be designed to recognize a lead candidate from a list to develop the procedure for scale-up, to choose the unsurpassed formulation, to determine the frequency, and duration of exposure; and eventually make the foundation of the anticipated clinical trial design. The foremost aim in the pharmaceutical research and industry is the claim of drug product quality throughout a drug's life cycle. The particulars of the pre-clinical development process for different candidates may vary; however, all have some common features. Typically in vitro, in vivo or ex vivo studies are elements of pre-clinical studies. Human pharmacokinetic in vivo studies are often supposed to serve as the 'gold standard' to assess product performance. On the other hand, when this general assumption is revisited, it appears that in vitro studies are occasionally better than in vivo studies in assessing dosage forms. The present review is compendious of different such models or approaches that can be used for designing and evaluation of formulations for nail delivery with special reference to anti-fungal agents. [ABSTRACT FROM AUTHOR]

Introduction: Topical drug delivery is highly attractive and yet faces tissue barrier challenges. Different physical and chemical methods have been explored to facilitate topical drug delivery., Areas Covered: Ablative fractional laser (AFL) has been widely explored by the scientific community and dermatologists to facilitate topical drug delivery since its advent less than two decades ago. This review introduces the major efforts in exploration of AFL to facilitate transdermal, transungual, and transocular drug delivery in preclinical and clinical settings., Expert Opinion: Most of the preclinical and clinical studies find AFL to be safe and highly effective to facilitate topical drug delivery with little restriction on physicochemical properties of drugs. Clinical studies support AFL to enhance drug efficacy, shorten treatment time, reduce pain, improve cosmetic outcomes, reduce systemic drug exposure, and improve safety. Considering most of the clinical trials so far involved a small sample size and were in early phase, future trials will benefit from enrolling a large group of patients for thorough evaluation of the safety and efficacy of AFL-assisted topical drug delivery. The manufacturing of small and less costly AFL devices will also facilitate the translation of AFL-assisted topical drug delivery.

Background: Glomus tumors are benign hamartomas arising from the glomus body, mostly occurring in the subungual region of the digits. A triad of excruciating pain, localized tenderness and cold sensitivity is the key to diagnosing these tumors. Two surgical approaches are described in the literature for excision of subungual glomus tumors-transungual and periungual. We reviewed retrospectively the results of subungual glomus tumors of the hand treated by transungual excision. Materials and Methods: Twelve patients (9 females and 3 males) with histopathologically confirmed subungual glomus tumors of the hand were treated by transungual excision at our institute. The mean age of the patients was 40.5 years (range 28-63 years). All patients presented with pain in the nail bed and cold sensitivity. A bluish-brown discoloration was present in 6 patients. Love's pin test was positive in all and Hildreth's test was positive in 8 patients. The mean duration of followup was 38 months (range 8-72 months). Results: All patients had complete pain relief. There was no new nail deformity and no recurrence till last followup. One patient had deformity of the nail preoperatively due to previous surgery, which persisted after excision of the tumor. All of them returned to their preoperative occupation and regained full function of the hand. Conclusions: The transungual approach provides good access to the entire lesion and facilitates complete excision. Contrary to reported literature, we did not find the development of any new nail deformity with this approach. [ABSTRACT FROM AUTHOR]

The human nail plate is a formidable barrier to drug permeation. Development of therapeutics for management of nail diseases thus remains a challenge. This article reviews the current knowledge and recent advances in the field of transungual drug delivery and provides guidance on development of topical/ungual therapeutics for management of nail diseases, with special emphasis on management of onychomycosis, the most common nail disease. Selection of drug candidates, drug delivery approaches, and evaluation of formulations are among the topics discussed. A comprehensive mathematical description for transungual permeation is also introduced. [ABSTRACT FROM AUTHOR]

The main objective of the current work is to demonstrate the process of passive lateral diffusion in the human nail plate and its effect on the passive transungual permeation of antifungal drug ciclopirox olamine (CPO). A water soluble dye, methyl red sodium salt (MR) was used to visualize the process of lateral diffusion using a novel suspended nail experiment. The decline in concentration of CPO correlates with that of concentration of MR from the proximal to the distal end of the nail in suspended nail study. Three toenails each were trimmed to 5 mm × 5 mm (25 mm), 7 mm × 7 mm (49 mm), and 9 mm × 9 mm (81 mm) to study the extent and effect of lateral diffusion of the CPO on its in vitro transungual permeation. The permeation flux of CPO decreased as the surface area of the toenail increased. There was a positive correlation between the concentrations of CPO and MR in the area of application and in the peripheral area of the toenails of the three surface areas, confirming the findings in the suspended nail experiment. Profound lateral diffusion of CPO was demonstrated and shown to reduce the in vitro passive transungual drug permeation and prolong the lag-time in human toenails. The study data implies that during passive in vitro transungual permeation experiments, the peripheral nail around the area of drug application has to be kept to a minimum, in order to get reliable data which mimics the in vivo situation. [ABSTRACT FROM AUTHOR]

Synopsis Although considered as trifling illness, nail diseases have a reasonably high occurrence and a noteworthy impact on the patients' quality of life. Furthermore, there is a need to improve the topical treatment for nail diseases to avoid drug interactions and to reduce side effects associated with oral therapy. Topical drug delivery to the nails has established amplified consideration lately. Strategies (such as chemical enhancers, formulation strategies, physical and mechanical methods) are being investigated in order to improve drug permeability across the nail plate. The rationale of this review is to present contemporary information on the structure of human nail along with its comparison with animal hooves. Precincts of nail permeability have been briefly discussed with respect to factors like permeant's molecular size, hydrophilicity, charge and the nature of the vehicle. These factors affect drug uptake and permeation through the nail. Formulations like nail lacquers which mimic cosmetic varnish and colloidal carriers along with nail substitutes that can be utilized for transungual delivery have also been discussed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate characteristics of transungual drug delivery and the feasibility of developing a drug-in-adhesive formulation of terbinafine. The permeation of terbinafine from a PSA matrix across porcine hoof membrane was determined using a plate containing poloxamer gel. The permeation rate of terbinafine across hairless mouse skin was evaluated using a flow-through diffusion cell system. The permeation of terbinafine across the hoof membranes was the highest from the silicone adhesive matrix, followed by PIB, and most of the acrylic adhesives, SIS, and SBS. The rank order of permeation rate across mice skin was different from the rank order across porcine hooves. The amount of terbinafine permeated across the porcine hoof membranes poorly correlated with the amount of terbinafine remaining inside the hooves after 20 days, however, the ratio between rate of terbinafine partitioning into the hoof membrane and its rate of diffusion across the membrane was relatively constant within the same type of PSA. For influence of various vehicles in enhancing permeation of terbinafine across the hoof membrane, all vehicles except Labrasol showed tendency to improve permeation rate. However, the enhancement ratio of a given vehicle differed from one adhesive to another with a moderate correlation between them. The infrared spectrum of the hoof treated with NMP, PPG 400 or PEG 200 indicated that the conformation of keratin changed from a non-helical to a helical structure. [ABSTRACT FROM AUTHOR]

Abstract: Drug delivery by topical route for the treatment of onychomycosis, a nail fungal infection, is challenging due to the unique barrier properties of the nail plate which imparts high resistance to the passage of antifungal drugs. Permeation enhancers are used in transungual formulations to improve the drug flux across the nail plate. Selection of the effective permeation enhancer among the available large pool of permeation enhancers is a difficult task. Screening the large number of permeation enhancers using conventional Franz diffusion cells is laborious and expensive. The objective of present study was to evolve a simple, accurate and rapid method for screening of transungual drug permeation enhancers based on the principle of hydration of nail plate. The permeation enhancer which affects the structural or physicochemical properties of nail plate would also affect their hydration capacity. Two screening procedures namely primary and secondary screenings were evolved wherein hydration and uptake of ciclopirox olamine by nail plates were measured. Hydration enhancement factor, HEF24 and drug uptake enhancement factor, UEF24 were determined for screening of 23 typical permeation enhancers. The Pearson''s correlation coefficient between HEF24 and UEF24 was determined. A good agreement between the HEF24 and UEF24 data proved the validity of the proposed nail plate hydration model as a screening technique for permeation enhancers. [Copyright &y& Elsevier]

Abstract: The human nail remains one of the most challenging membranes for formulation scientists to target and for clinicians to heal. Its formidable barrier properties are the primary reason that oral therapy remains the primary approach to manage ungual infections. This article considers the major structural properties underlying the excellent barrier function of the nail, with particular emphasis on the role of biophysical methods in advancing our knowledge of this appendage. Formulations currently available for management of ungual disease are discussed and their therapeutic efficacy is assessed. Finally, experimental strategies to enhance ungual permeation are reviewed and prospects for future developments in the field are considered. [Copyright &y& Elsevier]

Topical therapy is desirable in treatment of nail diseases like onychomycosis (fungal infection of nail) and psoriasis. The topical treatment avoids the adverse effects associated with systemic therapy, thereby enhancing the patient compliance and reducing the treatment cost. However the effectiveness of the topical therapies has been limited due to the poor permeability of the nail plate to topically applied therapeutic agents. Research over the past one decade has been focused on improving the transungual permeability by means of chemical treatment, penetration enhancers, mechanical and physical methods. The present review is an attempt to discuss the different physical and chemical methods employed to increase the permeability of the nail plate. Minimally invasive electrically mediated techniques such as iontophoresis have gained success in facilitating the transungual delivery of actives. In addition drug transport across the nail plate has been improved by filing the dorsal surface of the nail plate prior to application of topical formulation. But attempts to improve the trans-nail permeation using transdermal chemical enhancers have failed so far. Attempts are on to search suitable physical enhancement techniques and chemical transungual enhancers in view to maximize the drug delivery across the nail plate. [ABSTRACT FROM AUTHOR]

The route of antifungal drug entry into the nail plate and the underlying nail bed plays an important role in determining the efficacy of therapy. Oral antifungal agents reach the nail bed and nail plate by being ingested and achieving antifungal levels in the blood stream that are well in excess of the minimum inhibitory concentration. The reticular circulation at the distal end of the digit enables the drug to reach the nail bed, the proximal matrix and the lateral nail folds. The drug then diffuses into the proximal, ventral and lateral nail plate. The primary route of drug delivery for topical lacquers is transungual, with drug applied to the dorsal aspect of the nail plate and penetrating to the underlying nail bed. The new topical agents approved in the US for the treatment of onychomycosis are solutions with lower viscosity and increased nail penetration characteristics; therefore, these agents penetrate through the transungual route, but also through the space between the nail plate and the nail bed. This subungual route is an important method of drug delivery and is able to in part circumvent the thickness of the nail plate. [ABSTRACT FROM AUTHOR]

[Display omitted] A nail patch is an attractive option for the topical treatment of onychomycosis, although no product is commercially available. We previously identified optimal nail patch formulations for two anti-onychomycotic drugs, based on their properties, as well as those of the other patch components. In this paper, our aim was to further investigate the potential of the patch formulations as topical nail medicines, in particular, whether the drug-in-adhesive patches release drug which then permeates into and through the nail plate and show anti-fungal efficacy, and whether and to what extent they remain adhered to the human nail plate in vivo when tested over 2 week durations. In addition, the influence of the drug (amorolfine HCl, ciclopirox olamine) and PSA (Duro-Tak 2852 or Duro-Tak 202A) on these parameters was determined. We found that both the nature of the drug and of the PSA influenced in vitro drug release. The nature of the drug, but not that of the PSA, influenced ungual drug permeation through human nail clippings, with considerably greater (almost double) permeation for ciclopirox olamine, the smaller and less lipophilic molecule. In vivo residence, tested with 3 out of the 4 patches, excluding the patch where ciclopirox olamine degraded with time, showed greater residence on toenails compared to fingernails reflecting their far lesser exposure to environmental stresses during daily activities. In vivo residence was enhanced when the patch was cut to the shape of the nail, was applied at bedtime, and when a clear colourless nail varnish was applied on top of the patch to 'seal' it into place on the nail. Comparison of the patches indicated greater residence of Duro-Tak 202A containing patches over those containing Duro-Tak 2852. Amorolfine HCl in Duro-Tak 202A based patch also showed antifungal efficacy in contrast to Duro-Tak 2852-based patch, and is particularly promising for further development as a potential toenail medicine, remaining almost fully adhered to toenails for at least two weeks. [ABSTRACT FROM AUTHOR]

The novel itraconazole (ITZ) nail penetration enhancing self-emulsifying nanovesicles (ITZ-nPEVs) loaded in carboxymethyl fenugreek gum (CMFG) gel circumvent the systemic onychomycosis treatment. The ITZ-nPEVs were prepared by the thin film hydration technique, and the particle size (PS), zeta potential (ZP), drug content (DC), entrapment efficiency (% EE), deformity index (DI), viscosity, morphology, and physical stability of the ITZ-nPEVs were measured. In terms of nail hydration, transungual drug absorption, and antifungal efficacy against Candida albicans, the chosen ITZ-nPEVs, nPEV-loaded CMFG (CMFG-ITZ-nPEVs) gel, and the commercialized Itrostred gel were compared. The ITZ-nPEVs showed spherical structure with high DC, % EE, low PS and PDI and positive ZP of ITZ ranging from 95.36 to 93.89 mg/5 mL and 95.36–96.94%, 196.55–252.5 nm, 0.092–0.49, and +11.1 to +22.5 mV, respectively. Compared to the Itrostred gel, the novel ITZ-nPEVs exhibited hydration enhancement factor for 24 h (HE24) of 1.53 and 1.39 drug uptake enhancement factor into nail clippings. Moreover, zone of inhibitions for ITZ-nPEVs (27.0 ± 0.25 mm) and CMFG-ITZ-nPEVs (33.2 ± 0.09 mm) against Candida albicans were significantly greater than that of Itrostred gel (22.9 ± 0.44 mm). For clinical investigation on onychomycotic patients, a nail penetration enhancer containing ITZ-nPEV-loaded CMFG gel presents a highly promising approach. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effects of pH and ionic strength on electroosmotic transport in transungual iontophoresis. Transungual iontophoretic transport of model neutral permeants mannitol (MA) and urea (UR) across fully hydrated human nail plates in phosphate-buffered saline of different pH and ionic strengths were investigated in vitro. Two protocols were involved in the transport experiments with each protocol divided into stages including passive and iontophoresis transport at 0.1 and/or 0.3 mA. Nail plate electrical resistance and water uptake of nail clippings were measured at various pH and ionic strengths. In the pH study, electroosmosis enhanced the anodal transport of MA at pH 9 and cathodal transport at pH 3. The Peclet numbers of MA were more than two times higher than those of UR under these conditions. No significant electroosmosis enhancement was observed for MA and UR at pH 5. In the ionic strength study, a decrease in solution ionic strength from 0.7 to 0.04 M enhanced electroosmotic transport. Nail electrical resistance increased with decreasing the ionic strength of the equilibrating solution, but reached a plateau when the ionic strength was less than approximately 0.07 M. Solution pH and ionic strength had no significant effect on nail hydration. Under the studied pH and ionic strength conditions, the effects of electroosmosis were small compared to the direct-field effects in transungual iontophoretic transport of small to moderate size permeants. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5186–5197, 2008 [ABSTRACT FROM AUTHOR]

Transungual iontophoretic transport of model neutral permeants mannitol (MA), urea (UR), and positively charged permeant tetraethylammonium ion (TEA) across fully hydrated human nail plates at pH 7.4 were investigated in vitro. Four protocols were involved in the transport experiments with each protocol divided into stages including passive and iontophoresis transport of 0.1 and 0.3 mA. Water and permeant uptake experiments of nail clippings were also conducted to characterize the hydration and binding effects of the permeants to the nails. Iontophoresis enhanced the transport of MA and UR from anode to cathode, but this effect (electroosmosis) was marginal. The transport of TEA was significantly enhanced by anodal iontophoresis and the experimental enhancement factors were consistent with the Nernst–Planck theory predictions. Hindered transport was also observed and believed to be critical in transungual delivery. The barrier of the nail plates was stable over the time course of the study, and no significant electric field-induced alteration of the barrier was observed. The present results with hydrated nail plates are consistent with electrophoresis-dominant (the direct field effect) transungual iontophoretic transport of small ionic permeants with small contribution from electroosmosis. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 881–893, 2008 [ABSTRACT FROM AUTHOR]

Objectives: Vesicular drug delivery has become a useful approach for therapeutic administration of pharmaceutical compounds. Lipid vesicles have found application in membrane biology, immunology, genetic engineering and theragnostics. This review summarizes topical delivery, specifically dermal/transdermal, ocular and transungual, via these vesicles, including future formulation perspectives., Key Findings: Liposomes and their subsequent derivatives, viz. niosomes, transferosomes, pharmacososmes and ethosomes, form a significant part of vesicular systems that have been successfully utilized in treating an array of topical disorders. These vesicles are thought to be a safe and effective mode of improving the delivery of lipophilic and hydrophilic drugs., Summary: Several drug molecules are available for topical disorders. However, physicochemical properties and undesirable toxicity have limited their efficacy. Vesicular delivery systems have the potential to overcome these shortcomings due to properties such as high biocompatibility, simplicity of surface modification and suitability as controlled delivery vehicles. However, incorporating these systems into environmentally responsive dispersants such as hydrogels, ionic liquids and deep eutectic solvents may further enhance therapeutic prowess of these delivery systems. Consequently, improved vesicular drug delivery can be achieved by considering combining some of these formulation approaches., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Background: Onychomycosis is by far the most common finger or toe nail fungal infectious disease caused by dermatophytes, non-dermatophytic molds or yeast. It accounts for 50% of the total nail disorders, and affects patients physically, socially, and psychologically and can seriously influence their quality of life., Objectives: Oral antifungals are routinely used to treat the nail fungal disease; however oral therapy is associated with severe side effects and longer treatment times. In recent years, drug delivery directly into the nail or nail bed has gained attention and various topical products have been tested that can cure the disease when applied topically or transungually. Nevertheless, drug penetration into and through the nail is not straightforward and requires chemicals to improve its permeability or by applying physical stress to promote drug penetration into and through the nail. This lucid review presents an overview of various causes of onychomycosis, current therapeutic approaches, and efforts aimed at increasing the permeability of nails through various strategies such as chemical, physical and mechanical methods for permeation enhancement., Conclusion: Various strategies have been proposed for the treatment of onychomycosis, however, much research into a more precise and effective therapy is still required., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Onychomycosis is a fungal infection of nails that is widespread and difficult to treat because of the impermeable nature of human nails. Topically applied anti-fungal agents cannot penetrate this structure, and treatment regimens often resort to systemic antifungals with concomitant side effects. One recent clinical study suggested that mechanical fenestration of the nail using an intelligent nail drill might be a possible solution to this problem. In this work, an in vitro model of the transungual delivery of antifungal agents is presented, which utilizes real nail tissue and an inline flow system. This system was deployed to measure transungual delivery of ciclopirox and determined that nail fenestration improved drug delivery by 3⁻4-fold after 42 days. This study bolsters the argument that nail fenestration should be accepted as a pretreatment for onychomycosis and offers a way of evaluating new drugs or formulations designed to combat this condition.