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A Promising Strategy for the Treatment of Onychomycosis with Curcumin and Photodynamic Therapy


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Onychomycosis is a disease of high incidence in the nail plate and responsible for approximately half of the cases of nail infections. Conventionally, dermatologists prescribe antibiotics and antifungals for long periods for its treatment. The high incidence of this type of infection and the increase of microbial strains resistant to the available drugs have justified the importance of the development of new technologies and treatments. This paper presents the photodynamic therapy as an alternative treatment of onychomycosis. New strategies for the use of curcumin as a photosensitizer and its therapeutic response were investigated in different formulations (gel and emulsion). Photodynamic therapy is a promising technique by which microorganisms are eliminated by a photosensitizing compound , light and oxygen. It was evaluated in two patients who had developed lesions in the fingernails caused by onychomycosis for approximately 10 years. The lesions were treated by photodynamic therapy with curcumin. The therapeutic efficacy was observed after a maximum of six photodynamic therapy sessions without any other adjuvant therapy. Curcumin has become more promising than the therapeutic standard as it is a natural and versatible drug for incorporation in different formulations, at low cost and low probability of side effects.
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Journal of Pharmacy and Pharmacology 3 (2015) 434-437
doi: 10.17265/2328-2150/2015.09.005
A Promising Strategy for the Treatment of
Onychomycosis with Curcumin and Photodynamic
Ana Paula da Silva, Fernanda M. Carbinatto, Vanderlei S. Bagnato and Natalia M. Inada
University of Sao Paulo, Physics Institute of Sao Carlos, 13566-590 Sao Carlos, SP, Brazil
Abstract: Onychomycosis is a disease of high incidence in the nail plate and responsible for approximately half of the cases of nail
infections. Conventionally, dermatologists prescribe antibiotics and antifungals for long periods for its treatment. The high incidence
of this type of infection and the increase of microbial strains resistant to the available drugs have justified the importance of the
development of new technologies and treatments. This paper presents the photodynamic therapy as an alternative treatment of
onychomycosis. New strategies for the use of curcumin as a photosensitizer and its therapeutic response were investigated in
different formulations (gel and emulsion). Photodynamic therapy is a promising technique by which microorganisms are eliminated
by a photosensitizing compound , light and oxygen. It was evaluated in two patients who had developed lesions in the fingernails
caused by onychomycosis for approximately 10 years. The lesions were treated by photodynamic therapy with curcumin. The
therapeutic efficacy was observed after a maximum of six photodynamic therapy sessions without any other adjuvant therapy.
Curcumin has become more promising than the therapeutic standard as it is a natural and versatible drug for incorporation in different
formulations, at low cost and low probability of side effects.
Key words: Onychomycosis, photodynamic therapy, curcumin, formulations.
1. Introduction
Onychomycosis is a nail fungal infection caused by
dermatophytes, yeasts or nondermatophytes. Systemic
and topical antifungal agents can be used in its
conventional treatment [1, 2]. However, oral
antifungals may cause adverse effects. The topical
formulation with antifungal agents may have low
therapeutic efficacy because of their limited ability to
penetrate the nail plate and reach the affected area
[3].These factors and the high incidence of this
infection are important parameters for the analyses of
Corresponding author: Natalia M. Inada, Ph.D., doctor of
medical pathophysiology, post-doctorate by the physics
institute of USP in São Carlos (IFSC), researcher, research
fields: biology, medicine, pharmacy, chemistry and physics,
with a background in biochemistry (metabolism and
bioenergetics), operates mainly in: mitochondrial bioenergetics,
tumor cells, reactive oxygen species, cell death mechanisms,
basic photodynamic therapy (in vitro and in vivo) and applied
(clinical research), optical devices applied in health. E-mail:
new formulations associated with other techniques to
ensure the success of the therapy.
PDT (photodynamic therapy) is a noninvasive
simple technique, therefore it is an interesting therapy
for the treatment of onychomycosis. It is characterized
by the association of a photosensitizing agent and a
light source of suitable wavelength. When this
photosensitizer is activated by light in the presence of
oxygen, it produces reactive oxygen species that
inactivate the fungi and cause onychomycosis [4].
Curcumin is a component obtained from the rizoma
of Curcuma Longa Linn and investigated as a
potential PS (photosensitizing compound) in PDT for
the inactivation of microorganisms. Besides its use as
a PS, it can act on localized superficial infections.
Initially, curcumin was used mainly in the food
industry, but its application is not limited to the food
area. It has shown several biological effects, such as
suppression of carcinogenesis by avoiding the
A Promising Strategy for the Treatment of Onychomycosis with Curcumin and Photodynamic Therapy
proliferation of a wide variety of tumor cells (skin,
lung, stomach, colon and breast), anti-inflammatory,
antioxidant and bactericidal activitivies.
Pharmacological actions can be intensified when
curcumin is irradiated with blue light [5-7].
Silva, A. P. et al reported some promising results
regarding the use of curcumin solutions for
onychomycosis treatments in patients that had showed
unsatisfactory results in conventional therapies and
had been affected by the disease for more than 5 years.
The patients nail plates were applied a curcumin
solution and then illuminated with LED (light emitting
diode) 450 nm [8]. However, curcumin in solution
does not remain long in contact with the lesion due to
the limitation of its standard formulation. As the nail
plate is composed mainly of keratin, a low content of
lipids and water, it works as a hydrophilic barrier.
Lipids may represent an important route of
transportation mainly for hydrophobic substances [9].
As the nail plate hampers the permeation of the PS,
we have studied new formulations to improve the
success of the therapy with curcumin.
Due to the structural characteristics of the nail plate,
curcumin was used in different formulations
(hydrophilic gel and water/oil emulsion) for the
analysis of the success of the therapy.
2. Material and Methods
2.1 Patient Selection
The patients with onychomycosis were selected
with a clinical diagnosis confirmed by podiatrist.
The experiments were approved by the Ethics
Committee of Anhembi Morumbi University (79th
Ethics Committee Meeting on November 16, 2010)
and patients signed an informed consent.
2.2 Formulation with PS
Curcumin was solubilize with 1% alcohol and 0,1%
dimethyl sulfoxide after Curcumin was incorporated
in the 1.5% concentration in two different formulation,
in carbopol gel and emulsion W/O.
2.3 PDT for Treatment Onycomycosis
Patients with Onychomycosis were treated for 20
min by an LED (450 nm, 100 mW/cm²) system
developed in the Laboratory of Technological Support
and anatomically designed for fingernails and
Toenails (total fluence of 120 J/cm²) (Fig. 1).
Patients had their nail plate prepared with a solution
of 40% urea emollient two hours before the treatment.
Urea was in contact with the nail for one hour and
after this period its excess was removed and PS was
applied for one hour before illumination.
Curcumin in the 1.5% concentration was topically
applied in gel or emulsion and subjected to
illumination. After a seven-day treatment, a new
evaluation was conducted for the analysis of the
clinical response to the treatment. The follow-up
treatment was performed by a clinical evaluation and
documented by photographic images weekly.
For a comparative analysis of different formulations,
the treatment was performed in two patients (case 1:
male, aged 27 and case 2: female, 65 years old) with
Fig. 1 Design of the device registered in the National Institute of Industrial Property (INPI Protocol No. 18110047225,
December 5th, 2011).
A Promising Strategy for the Treatment of Onychomycosis with Curcumin and Photodynamic Therapy
fingernail diseases caused by fungi. Both patients had
had the lesions for approximately 10 years. The results
were positive for the laboratory cultures, which
indicated the presence of fungi.
3. Results
3.1 Patient 1: Treatment of Onychomycosis with Gel
Gel curcumin (1.5%) was topically applied to the
fingernail (Fig. 2) in case 1. The nail was then
protected from light for 1h. Only 6 PDT sessions were
applied and a complete healing was achieved (Fig. 2b)
and evidenced by the negative culture of
microorganisms for fungi that cause onychomycosis.
3.2 Patient 2: Treatment of Onychomycosis with
Emulsion Curcumin
Curcumin incorporated in emulsion (1.5%) was
topically applied to the fingernail (Fig. 3) in case 2.
The nail was then protected from light for 1h. Only 5
PDT sessions were necessary and a complete healing
was achieved (Fig. 3b) and evidenced by the negative
culture of microorganisms for fungi that cause
Fig. 2 Male patient, 10 years of lesion, (a) before treatment and (b) after 6 sessions of PDT with curcumin (PDT pharma gel
Fig. 3 Female patient, 10 years of lesion, (a) before treatment and (b) after 5 sessions of PDT with curcumin (PDT Pharma
Emulsion 1.5%).
A Promising Strategy for the Treatment of Onychomycosis with Curcumin and Photodynamic Therapy
4. Discussions
This study has demonstrated the efficacy of PDT
with curcumin as a photosensitizer agent in the
treatment of onychomycosis. The possibility of using
vehicular curcumin in different formulations (gel and
emulsion) can be a positive aspect for this approach.
The new formulation combined with the
pre-treatment of the nail bed, can favor the penetration
of curcumin in the lesion. The patients reported no
pain during and after the treatment and the sessions
were repeated weekly.
The satisfactory results achieved with few treatment
sessions have proven the differential of this new
approach to treat onychomycosis in comparison to
conventional treatments, which require a higher
number of sessions and may cause discontinuity of the
5. Conclusion
Photodynamic therapy has shown increased
potential to aid in microbial and fungal reductions . It
was possible to reach a favorable setting for
commercial viability of the formulations developed
for clinical research, which should help to expedite the
availability of this technique to the national and
international clinical reality. PDT using different
formulation with curcumin is a technique with great
potential and low-cost treatment of onychomycosis.
This research has been supported by grants from
Fundacão de Amparo à Pesquisa do Estado de São
Paulo (FAPESP; CEPOF Grant No. 98/14270-8) and
Financiadora de Estudos e Projeto FINEP-Gnatus
(Grant No. 554339/2010-2). APS was supported by
Conselho Nacional de Desenvolvimento Científico e
Tecnológico (CNPq FINEP-Gnatus; GrantNo.
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... One of the most explored and successful clinical applications of PDI is in the treatment of nail onychomycosis, as was extensively discussed in several reviews [260][261][262]. We included in Table 9 some of the most successful examples of PDDI using 5-ALA [249,250], curcumin [251], and methylene blue [253,254]. Multiple treatments are necessary. ...
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Photodynamic therapy is witnessing a revival of its origins as a response to the rise of multi-drug resistant infections and the shortage of new classes of antibiotics. Photodynamic disinfection (PDDI) of microorganisms is making progresses in preclinical models and in clinical cases, and the perception of its role in the clinical armamentarium for the management of infectious diseases is changing. We review the positioning of PDDI from the perspective of its ability to respond to clinical needs. Emphasis is placed on the pipeline of photosensitizers that proved effective to inactivate biofilms, showed efficacy in animal models of infectious diseases or reached clinical trials. Novel opportunities resulting from the COVID-19 pandemic are briefly discussed. The molecular features of promising photosensitizers are emphasized and contrasted with those of photosensitizers used in the treatment of solid tumors. The development of photosensitizers has been accompanied by the fabrication of a variety of affordable and customizable light sources. We critically discuss the combination between photosensitizer and light source properties that may leverage PDDI and expand its applications to wider markets. The success of PDDI in the management of infectious diseases will ultimately depend on the efficacy of photosensitizers, affordability of the light sources, simplicity of the procedures, and availability of fast and efficient treatments. Graphic abstract
... It is also of great compatibility with human tissues and has good penetrability, allowing decontamination even for an internal portion of the contaminated layers of the wounds. There are several studies that indicate curcumin as an excellent option for use as a microbicide in PDT [40,41]. ...
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Healing wounds represent a major public health problem, mainly when it is infected. Besides that, the antibiotics misuse and overuse favor the development of bacterial resistance. This study evaluated the effects of antimicrobial photodynamic therapy (aPDT) combined with artificial skin on disinfection of infected skin wound in rats. Twenty-four Wistar rats were randomly distributed into 4 groups (n = 6): (i) control—untreated; (ii) aPDT—treated with curcumin-mediated aPDT (blue light); (iii) artificial skin—treated with artificial skin alcohol-based; and (iv) aPDT plus artificial skin—treated with aPDT associated with artificial skin alcohol-based. For the in vivo model, a full-thickness biopsy with 0.80 cm was performed in order to inoculate the microorganism Staphylococcus aureus (ATCC 25923). The aPDT was performed with a curcumin gel and a blue LED light (450 nm, 80 mW/cm²) at the dose of 60 J/cm² and the treatment with alcohol-based artificial skin was done with the topical application of 250 μL. Additional animals were submitted to aPDT combined with the artificial skin. After treatments, the number of colony-forming units (CFU) and the damage area were determined. Data were analyzed by two-way repeated measures ANOVA and Tukey tests. The highest reduction of the bacterial viability was observed in the PDT plus artificial skin group (4.14 log10), followed by artificial skin (2.38 log10) and PDT (2.22 log10) groups. In addition, all treated groups showed higher relative area of wound contraction (36.21% for the PDT, 38.41% for artificial skin, and 35.02% for PDT plus artificial) in comparison with the control group. These findings provide evidence for the positive benefits of aPDT with blue light and curcumin associated with artificial skin to decontaminate and accelerate the wound contraction.
Photodynamic therapy is an alternative treatment mainly for cancer but also for bacterial infections. This treatment dates back to 1900 when a German medical school graduate Oscar Raab found a photodynamic effect while doing research for his doctoral dissertation with Professor Hermann von Tappeiner. Unexpectedly, Raab revealed that the toxicity of acridine on paramecium depends on the intensity of light in his laboratory. Photodynamic therapy is therefore based on the administration of a photosensitizer with subsequent light irradiation within the absorption maxima of this substance followed by reactive oxygen species formation and finally cell death. Although this treatment is not a novelty, there is an endeavor for various modifications to the therapy. For example, selectivity and efficiency of the photosensitizer, as well as irradiation with various types of light sources are still being modified to improve final results of the photodynamic therapy. The main aim of this review is to summarize anticancer and antibacterial modifications, namely various compounds, approaches, and techniques, to enhance the effectiveness of photodynamic therapy.
Background: This systematic review aimed to investigate the effectiveness of CUR-mediated PDT (Curcumin mediated PDT) as an adjunct to conventional chemo-mechanical debridement and/or standard PDT of the RC system with endodontic infections. Methods: The focused research question was: "Whether the application Curcumin mediated PDT as an adjunct is more effective than the traditional chemo-mechanical debridement and/or standard PDT of the RC system alone for improving antibacterial and/or mechanical features among subjects undergoing RCT?". An electronic literature search was performed in Scopus, PubMed, and Web of Science. In vitro reports utilizing Curcumin mediated PDT as an adjunct to conventional chemo-mechanical debridement considering permanent dentition assessing the antibacterial and/or mechanical effect were included. Results: Eighteen articles were included in the review, out of which 13 studies assessed the antibacterial activity, while 5 evaluated the mechanical properties. Most of the studies concluded that Curcumin mediated PDT had a significant antibacterial activity than the conventional chemo-mechanical debridement and/or standard PDT. Four of the five studies suggested that Curcumin mediated PDT had no impact on the push-out bond strength of root dentin. Furthermore, the significant heterogeneity in the data from the included studies did not permit the author to carry out a meta-analysis. Conclusion: There is potential for application of Curcumin mediated PDT as an adjunct to the conventional chemo-mechanical debridement and/or standard PDT in reducing the bacterial load, however, Curcumin mediated PDT has minimal effect on enhancing the pushout bond strength of fiber posts to radicular dentin. Moreover, clinical studies are required to provide a more conclusive opinion on the efficacy of Curcumin mediated PDT for RCT procedures.
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Onychomycosis is a nail infection caused by a fungus, Trichophyton mentagrophytes, that is responsible for major nail infections. The best method suited for treating such infections generally includes a topical remedy. However, conventional oral or topical formulations are associated with various limitations. Therefore, a more efficient and compatible formulation is developed in this study. The primary objective of the current study is to formulate and evaluate chitosan nanoparticle-based hydrogel for ameliorating onychomycosis. The sole purpose of this research was to increase the permeation of the lipophilic drug itraconazole and difluorinated curcumin, and its synergistic antifungal activity was also evaluated for the first time. Both in vitro and ex vivo drug release evaluations confirmed the sustained release of both drugs from the hydrogel, which is a prerequisite for treating onychomycosis. The results overall highlighted the promising activity of a synergistic approach that could be implemented for the treatment of onychomycosis. The hydrogel-based formulation serves as an effective method of delivery of drugs across the layers of the skin, resulting from its hydrating characteristics.
Tinea capitis is a common scalp dermatophyte infection in children. Treatment necessitates oral antifungal therapy which represents a therapeutic challenge. Photodynamic therapy (PDT) has emerged as a new antifungal therapeutic approach. The efficacy of PDT depends on the proper choice of the photosensitizer and its delivery system. Curcumin, a natural polyphenol, is well studied as a photosensitizer, however, its hydrophobicity hinders its clinical use. This study aims to improve the use of curcumin in PDT by loading it to a novel vesicular nano spanlastics (NVS) and examine their efficacy in PDT of tinea capitis. A prospective, randomized, controlled comparative study was conducted. Fifty-two children with Tinea Capitis were randomly divided into four groups; Cur-PDT group, oral griseofulvin group, topical curcumin group, and blue light group. Clinical and dermoscopic assessments were done, at baseline, every two weeks and after 6 months for follow-up. The results were confirmed by potassium hydroxide (KOH) 10% and fungal culture before and after the treatment. Complete cure was based on clinical, dermoscopic, and mycological cures. Cur-PDT group showed complete clearance in 46% of children with variable response among fungal species, compared to 100% in the griseofulvin group. No effects were observed in curcumin or light groups. Cur-PDT group showed very mild tolerable burning pain. Griseofulvin group experienced systemic side effects in some cases. Cur-PDT can be a promising well-tolerated alternative treatment of tinea capitis, but with variable responses among fungal species.
Onychomycosis is an infection caused by a fungus that causes discoloration and thickening of the nail layer, and it is the most common nail infection in the world. Trichophyton rubrum and Trichophyton mentagrophytes var. interdigital is the most common anthropophilic dermatophytes that trigger it. Onychomycosis is caused by yeasts such as Candida albicans and Candida parapsilosis, as well as moulds such as Aspergillus spp. Treatment is determined by the type of nail invasion, the fungus genus, and the number of nails affected. Approaches towards conventional methods showed certain drawbacks which emphasizes the need for alternate approaches to produce better therapeutic efficacy of a product. The present review focused on reporting an updated classification of Onchyomycosis, causative organisms, factors influencing drug permeation, novel treatment strategies for Onychomycosis, drug permeation enhancement methods.
Background Photodynamic therapy (PDT) activates a photosensitizer by visible light to generate cytotoxic oxygen species that lead to cell death. With proper illumination, PDT is often used in applications on superficial and sub-surface lesions. Sporotrichosis infection occurs by Sporothrix fungi which causes a skin wound, worsened by Candida albicans infections. This study investigated the photosensitizing efficiency of the Ru(phen)2(pPDIp)(PF6)2 complex, RupPDIp, against S. brasiliensis and C. albicans. Material and methods RupPDIp efficiency against these fungi was tested using 450 nm (blue light and 36 J/cm²) and 525 nm (green light, 25.2 J/cm²) at 0.05–20 μM concentrations. To ensure PDT effectiveness, control groups were tested in the absence and in the presence of RupPDIp under light irradiation and in the dark. Results RupPDIp eliminated both fungi at ≤5.0 μM. Green light showed the best results, eliminating S. brasiliensis and C. albicans colonies at RupPDIp 0.5 μM and 0.05 μM, respectively. Conclusion RupPDIp is a promising photosensitizer in aPDT, eliminating 10⁶ CFU/mL of both fungi at 450 nm and 525 nm, with lower light doses and concentrations when treated with the green light compared to the blue light.
With rapid emergence of multi-drug resistant microbes, it is imperative to seek alternative means for infection control. Optical waveguides are an auspicious delivery method for precise administration of phototherapy. Studies have shown that phototherapy is promising in fighting against a myriad of infectious pathogens (i.e. viruses, bacteria, fungi, and protozoa) including biofilm-forming species and drug-resistant strains while evading treatment resistance. When administered via optical waveguides, phototherapy can treat both superficial and deep-tissue infections while minimizing off-site effects that afflict conventional phototherapy and pharmacotherapy. Despite great therapeutic potential, exact mechanisms, materials, and fabrication designs to optimize this promising treatment option are underexplored. This review outlines principles and applications of phototherapy and optical waveguides for infection control. Research advances, challenges, and outlook regarding this delivery system are rigorously discussed in a hope to inspire future developments of optical waveguide-mediated phototherapy for the management of infection and beyond.
Bacteria within biofilm display resistance to host defense and conventional antimicrobial agents. The present study was aimed to reduce biofilm formation by Staphylococcus aureus and Pseudomonas aeruginosa using photodynamic therapy. Natural photosensitizers such as curcumin and phycocyanin were encapsulated within chitosan nanoparticles synthesized by ionic gelation method. It was characterized by SEM, TEM, Particle size analyzer, UV-Vis analysis, FTIR, XRD and TGA. The antibacterial activity of curcumin and phycocyanin delivered through chitosan nanoparticles against S. aureus and P. aeruginosa was investigated by well diffusion assay. Photodynamic antibiofilm activity was investigated by crystal violet assay. Generation of reactive oxygen species by photosensitizers was recorded using spectrophotometer. The chitosan nanoparticles encapsulated with photosensitizers were spherical in shape with an average size of 20 nm. Encapsulation efficiency of chitosan nanoparticles was 36.45% for phycocyanin and 44.96% for curcumin. The antibacterial and antibiofilm activity of curcumin and phycocyanin increased with concentration. Curcumin and phycocyanin reduced less than 0.5% of biofilm formed by S. aureus and P. aeruginosa in dark treatment. Illumination reduced 2.57% and 2.18% of biofilm formed by S. aureus and P. aeruginosa respectively. Photodynamic activity of curcumin and phycocyanin delivered through chitosan nanoparticles at 100 _g/mL reduced 92% and 88% of biofilm formed by S. aureus and P. aeruginosa respectively. The dose dependent photodynamic antibacterial activity was found to be mediated through the formation of reactive oxygen species. The viability of fibroblast cells was 90% in phycocyanin, 85% in curcumin, 98.5% in sham control CNPs and 88% in CNPs encapsulated with PS at 80 _g/mL. Thus, the study demonstrated the significant reduction of biofilm formed by clinical isolates through photodynamic therapy without detrimental effect to human fibroblast cells.
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Context: Bacterial resistance to antibiotics is increasing and alternative antibacterial treatments like antimicrobial photodynamic therapy (aPDT) are needed. Curcumin is under investigation as a potential photosensitizer in aPDT. Objective: The purpose of this study was to develop rapidly dissolving formulations of curcumin that could photoinactivate both Gram-positive and Gram-negative bacteria. Materials and methods: Curcumin solid dispersions with methyl-β-cyclodextrin and hyaluronic acid (HA), hydroxypropyl methylcellulose (HPMC) or both HA and HPMC were prepared through lyophilization. The lyophilizates were characterized by curcumin drug load [% (w/w)], differential scanning calorimetry, photostability, thermal stability, their ability to form supersaturated solutions and by in vitro photoinactivation of Enterococcus faecalis and Escherichia coli. Results and discussion: The lyophilizates were amorphous solid dispersions with a curcumin drug load in the range of 1.4-5.5% (w/w) depending on the included polymer and the ratio between curcumin and the cyclodextrin. The lyophilizates were photolabile, but thermally stable and dissolved rapidly in contact with water to form supersaturated solutions. Selected lyophilizates demonstrated >log 6 reduction of colony forming units/ml of both E. faecalis and E. coli after exposure to low curcumin concentrations (0.5-10 µM) and blue light dose (11-16 J/cm(2)). The high drug load of the lyophilizates, rapid dissolution, ability to form relatively stable supersaturated solutions and the very high phototoxicity towards both E. faecalis and E. coli make these lyophilizates suitable for in vivo aPDT. Conclusions: This treatment with optimized curcumin formulations should be explored as an alternative to topical antibiotics in the treatment of wound infections.
Onychomycosis is the most common nail disorder. The treatment for this type of infection is one of the main difficult ones in clinical practice, due to the fact that the nails are nonvascularized structures, which compromise the penetration of drugs delivered systemically and favor slow nail growth. We present two devices based on light-emitting diode arrays as light sources for the treatment of onychomycosis by photodynamic therapy (PDT). PDT is an emerging technique that uses a photosensitizer (PS) activated by light in the presence of oxygen. The PS absorbs energy from light and transfers it to oxygen, producing reactive oxygen species such as hydroxyl radicals, superoxide, and singlet oxygen which inactivate fungi and bacteria. Our proposal is the use of a portable and secure light source device in patients with onychomycosis. Additional advantages are the low cost involved, the possibility of topical treatment rather than systemic and the simplicity of operation. These advantages are important to ensure the implementation of this technology for the treatment of an impacting health problem.
Traditional pharmacotherapy for onychomycosis has low to moderate efficacy and may be associated with adverse reactions and medication interactions limiting its use in many patients. We evaluated the clinical efficacy and safety of a fractional carbon-dioxide laser with topical antifungal therapy in the treatment of onychomycosis. In all, 24 patients were treated with fractional carbon-dioxide laser therapy and a topical antifungal cream. The laser treatment consisted of 3 sessions at 4-week intervals. Efficacy was assessed based on the response rate from standardized photographs, a microscopic examination of subungual debris, and subjective evaluations. Among the patients, 92% showed a clinical response and 50% showed a complete response with a negative microscopic result. The factors that influenced a successful outcome were the type of onychomycosis and the thickness of the nail plate before treatment. The treatment regimen was well tolerated and there was no recurrence 3 months after the last treatment episode. The study followed up only 24 patients and there were no relevant treatment controls. Fractional carbon-dioxide laser therapy, combined with a topical antifungal agent, was effective in the treatment of onychomycosis. It should be considered an alternative therapeutic option in patients for whom systemic antifungal agents are contraindicated.
The penetration behavior into human nails and animal hoof membranes of a novel antifungal agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established.
There have been many developments reported in the literature regarding treatment of nail psoriasis, melanonychia striata, and onychomycosis. For psoriasis, the efficacy and safety of intralesional corticosteroids and topical application of tazarotene, calcipotriol, and anthralin are discussed in recent clinical trials. With regard to melanonychia striata, the features differentiating benign from malignant entities, management algorithms, and treatment alternatives are reviewed. The efficacy and safety of itraconazole, terbinafine, and fluconazole are compared and evaluated in recent investigations for treatment of onychomycosis in children and adults.
The absorption of drugs into the nail unit, following topical application to the nail plate, is highly desirable to treat nail disorders, such as onychomycosis (fungal infections of the nail). Nail permeability is however quite low and limits topical therapy to early/mild disease states. In this paper, the recent research into ungual drug delivery is reviewed. The nail unit and the two most common diseases affecting the nail--onychomycosis and nail psoriasis--are briefly described to set the scene and to give an overview of the nature and scope of the problem. The factors, which affect drug uptake and permeation through the nail plate such as solute molecular size, hydrophilicity/hydrophobicity, charge, and the nature of the vehicle, are then discussed, followed by ways of enhancing drug transport into and through the nail plate. Finally, drug-containing nail lacquers which, like cosmetic varnish, are brushed onto the nail plates to form a film, and from which drug is released and penetrates into the nail, are reviewed.
Natural curcumin was evaluated as a potential photosensitizer for oral applications. The photocytotoxicity of curcumin on salivary gland acinar cells (SM 10-12) was investigated in five aqueous preparations consisting of 5% DMSO, non-ionic micelles, cyclodextrin, liposomes, or a hydrophilic polymer. The difference in phototoxic effects between natural curcumin and synthetic curcumin was examined. Cytotoxicity in SM 10-12 cells exposed to curcumin in the concentration range 0.4-13.5 microM was investigated by MTT test, a fluorescence-staining microscopic test, and by Western immunoblotting techniques. The potential formation of a photoreaction product, hydrogen peroxide, was evaluated by a fluorescence assay. The light source was a halogen lamp used in the dental clinic, emitting mainly in the blue part of the spectrum. The phototoxic effect on SM 10-12 cells was dependent on curcumin concentration, the light dose and the type of preparation. Natural and synthetic curcumin induced phototoxicity to the same extent. Significant effects on the cells were obtained at low curcumin concentrations (< or =0.5 microM) and at a low light dose (< or =6 J cm(-2)), after 3 h incubation. Neither the activation of caspases-3, -7, -8 or -9, nor the formation of hydrogen peroxide could be detected in cells exposed to curcumin and light. The liposome preparation was the most efficient vehicle for curcumin to induce cell death. The phototoxic effect induced by curcumin is highly dependent on the type of preparation. Curcumin might be a potential photosensitizer in the treatment of oral lesions and cancers provided careful selection of the vehicle.
  • E M Bruzell
  • E Morisbak
  • H H Tønnesenet
Bruzell, E. M., Morisbak, E., and Tønnesenet, H. H. 2005. " Studies on Curcumin and Curcuminoids. XXIX.