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What is skin fungal infection. Vesicular Nanocarriers: Revolutionizing Skin Fungal Infection Treatments

by alexxlab

What are vesicular nanocarriers. How do they improve treatment of skin fungal infections. What are the emerging trends in nanoscale pharmacotherapy for fungal skin diseases. What advantages do nanocarriers offer over traditional antifungal formulations.

Understanding Skin Fungal Infections: Causes and Prevalence

Skin fungal infections, also known as dermatomycoses, are a common health concern affecting millions of people worldwide. These infections are caused by various types of fungi, including dermatophytes, yeasts, and molds. The prevalence of skin fungal infections has been on the rise, particularly in immunocompromised individuals and those living in tropical climates.

What are the most common types of skin fungal infections? The most prevalent forms include:

  • Athlete’s foot (tinea pedis)
  • Ringworm (tinea corporis)
  • Jock itch (tinea cruris)
  • Candidiasis
  • Onychomycosis (fungal nail infections)

These infections can cause significant discomfort, including itching, redness, scaling, and in severe cases, can lead to secondary bacterial infections. The impact on quality of life and the economic burden of treatment make skin fungal infections a critical area of research in dermatology and pharmacology.

Challenges in Traditional Antifungal Therapies

Conventional treatments for skin fungal infections have long relied on topical and oral antifungal agents. However, these traditional approaches often face several limitations:

  • Poor skin penetration of topical formulations
  • Limited efficacy due to inadequate drug concentrations at the infection site
  • Systemic side effects of oral medications
  • Development of drug resistance in fungal strains
  • Prolonged treatment duration leading to poor patient compliance

Why do traditional antifungal treatments often fail? The primary reason is the inability of conventional formulations to effectively penetrate the stratum corneum, the outermost layer of the skin. This barrier function of the skin, while crucial for protection against external threats, also impedes the delivery of therapeutic agents to the site of infection.

Moreover, the emergence of drug-resistant fungal strains has further complicated treatment strategies, necessitating the development of novel approaches to combat these persistent infections.

The Rise of Vesicular Nanocarriers in Antifungal Therapy

In recent years, the field of nanomedicine has offered promising solutions to overcome the limitations of traditional antifungal treatments. Vesicular nanocarriers have emerged as a game-changing technology in the realm of topical drug delivery, particularly for the treatment of skin fungal infections.

What are vesicular nanocarriers? These are microscopic vesicles composed of lipid bilayers that encapsulate drug molecules. The most common types of vesicular nanocarriers include:

  • Liposomes
  • Niosomes
  • Transfersomes
  • Ethosomes
  • Phytosomes

How do vesicular nanocarriers enhance antifungal therapy? These innovative drug delivery systems offer several advantages:

  1. Improved skin penetration: The nano-sized vesicles can easily traverse the stratum corneum, delivering the antifungal agent directly to the site of infection.
  2. Controlled drug release: Nanocarriers can be designed to release the encapsulated drug over an extended period, maintaining therapeutic concentrations for longer durations.
  3. Enhanced stability: Encapsulation protects the antifungal agent from degradation, increasing its shelf life and efficacy.
  4. Reduced side effects: By targeting the drug specifically to the infection site, systemic exposure and associated side effects are minimized.
  5. Potential for combination therapy: Multiple drugs can be encapsulated within a single nanocarrier, allowing for synergistic effects and combating drug resistance.

Liposomes: Pioneering Vesicular Nanocarriers in Antifungal Treatment

Among the various types of vesicular nanocarriers, liposomes have been at the forefront of research and development in antifungal therapy. These spherical vesicles, composed of phospholipid bilayers, have shown remarkable potential in enhancing the efficacy of topical antifungal treatments.

What makes liposomes particularly suitable for antifungal drug delivery? Several factors contribute to their effectiveness:

  • Biocompatibility: Liposomes are made from natural phospholipids, similar to cell membranes, ensuring high biocompatibility and low toxicity.
  • Versatility: They can encapsulate both hydrophilic and hydrophobic drugs, making them suitable for a wide range of antifungal agents.
  • Fusogenic properties: Liposomes can fuse with fungal cell membranes, facilitating direct drug delivery into the pathogen.
  • Customizable surface properties: The liposomal surface can be modified to enhance skin penetration or target specific fungal species.

Studies have demonstrated the superior efficacy of liposomal formulations of antifungal drugs such as amphotericin B, fluconazole, and ketoconazole compared to their conventional counterparts. These formulations have shown improved skin penetration, higher local drug concentrations, and enhanced antifungal activity against various fungal species.

Niosomes and Transfersomes: Advanced Vesicular Systems for Enhanced Skin Penetration

While liposomes have paved the way for nanocarrier-based antifungal therapy, newer vesicular systems like niosomes and transfersomes have shown even greater potential in overcoming the skin barrier.

What are niosomes and how do they differ from liposomes? Niosomes are non-ionic surfactant-based vesicles that offer several advantages:

  • Higher stability compared to liposomes
  • Lower cost of production
  • Ability to enhance the stability of encapsulated drugs
  • Improved skin penetration due to their non-ionic nature

Transfersomes, on the other hand, are ultra-deformable liposomes that can squeeze through small pores in the skin. What makes transfersomes unique in antifungal therapy?

  • Exceptional skin penetration abilities, even reaching deeper layers of the skin
  • Ability to carry larger payloads of drugs compared to conventional liposomes
  • Potential for transdermal delivery of antifungal agents

Both niosomes and transfersomes have shown promising results in preclinical studies, demonstrating enhanced antifungal efficacy and improved skin penetration of drugs like terbinafine, clotrimazole, and econazole.

Ethosomes and Phytosomes: Harnessing the Power of Natural Compounds

The quest for more effective and safer antifungal treatments has led to the development of ethosomes and phytosomes, two innovative vesicular systems that leverage the properties of ethanol and plant-based compounds, respectively.

What are ethosomes and how do they enhance antifungal therapy?

  • Ethosomes are phospholipid vesicles containing high concentrations of ethanol
  • The presence of ethanol increases the fluidity of skin lipids, enhancing drug penetration
  • They can encapsulate both hydrophilic and lipophilic molecules
  • Ethosomal formulations have shown superior antifungal activity compared to conventional creams and gels

Phytosomes, on the other hand, combine the benefits of herbal extracts with the advanced drug delivery capabilities of phospholipid vesicles. How do phytosomes contribute to antifungal therapy?

  • They enhance the bioavailability of plant-based antifungal compounds
  • Phytosomes can improve the stability and absorption of herbal extracts
  • They offer a potentially safer alternative to synthetic antifungal agents
  • Phytosomal formulations of compounds like curcumin and silymarin have shown promising antifungal activity

The combination of natural antifungal compounds with advanced vesicular delivery systems opens up new possibilities for developing effective and well-tolerated treatments for skin fungal infections.

Emerging Trends in Nanoscale Pharmacotherapy for Fungal Skin Diseases

As research in the field of vesicular nanocarriers continues to advance, several exciting trends are emerging that promise to revolutionize the treatment of skin fungal infections:

  1. Smart nanocarriers: Development of stimuli-responsive vesicles that release their drug payload in response to specific triggers such as pH changes or enzymatic activity at the infection site.
  2. Combination therapy: Encapsulation of multiple antifungal agents or combining antifungal drugs with penetration enhancers to achieve synergistic effects.
  3. Targeted delivery: Functionalization of nanocarriers with ligands that specifically bind to fungal cell surfaces, improving the selectivity and efficacy of treatment.
  4. Nanotechnology-enabled diagnostic tools: Integration of diagnostic capabilities into nanocarrier systems for simultaneous detection and treatment of fungal infections.
  5. Personalized medicine: Tailoring nanocarrier formulations based on individual patient characteristics and specific fungal strains to optimize treatment outcomes.

These emerging trends highlight the potential of nanoscale pharmacotherapy to not only enhance the efficacy of existing antifungal agents but also to develop entirely new approaches to treating fungal skin diseases.

Overcoming Challenges and Future Perspectives

While vesicular nanocarriers offer immense potential in revolutionizing antifungal therapy, several challenges need to be addressed to fully realize their clinical potential:

  • Scale-up and manufacturing: Developing cost-effective and reproducible large-scale production methods for nanocarrier formulations.
  • Stability: Ensuring long-term stability of nanocarriers under various storage conditions.
  • Regulatory hurdles: Navigating the complex regulatory landscape for nanomedicine-based products.
  • Safety concerns: Conducting comprehensive long-term safety studies to address potential toxicity issues associated with nanocarriers.
  • Clinical translation: Bridging the gap between promising preclinical results and successful clinical outcomes.

Despite these challenges, the future of vesicular nanocarrier-based treatments for skin fungal infections looks promising. As researchers continue to innovate and refine these technologies, we can anticipate:

  • More effective and targeted antifungal therapies with reduced side effects
  • Shorter treatment durations, leading to improved patient compliance
  • Novel combination therapies that address drug resistance
  • Integration of nanotechnology with other emerging fields like artificial intelligence for personalized treatment strategies

The ongoing research in this field is paving the way for a new era in the management of skin fungal infections, offering hope to millions of patients worldwide who suffer from these persistent and often debilitating conditions.

Conclusion

Vesicular nanocarriers represent a significant leap forward in the treatment of skin fungal infections. By addressing the limitations of traditional antifungal therapies, these innovative drug delivery systems offer the potential for more effective, targeted, and patient-friendly treatments. As research in this field continues to evolve, we can expect to see increasingly sophisticated and personalized approaches to managing fungal skin diseases, ultimately improving patient outcomes and quality of life.

Vesicular nanocarrier based treatment of skin fungal infections: Potential and emerging trends in nanoscale pharmacotherapy

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Getting Under Your Skin: How A Fungus Takes Hold

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Written by Heather Davies-Strickleton, Senior Analytical Scientist

We are not alone in this world. Although we can’t see them, we share our surroundings with billions of tiny microscopic organisms (microbes). Like us, they’re looking for a cosy place to live, survive and thrive. And the place that many of them like to call home is actually us – the human body! While many of these microbes help us, there are some that we could just live without.

Not such a fun guy to have around is a type of microbe called a dermatophyte (from Greek δέρμα derma (skin) and φυτόν phyton “plant”). Dermatophytes are filamentous fungi in the genera of Trichophyton, Microsporum and Epidermophyton, which can invade our skin, hair and nail to cause irritating, highly-infectious rashes (e.g. ringworm and Athlete’s foot), hair loss (e.g. ringworm of the scalp) and flaky, discoloured nails (e.g. fungal nail disease).1

Dermatophytes achieve this because they live off keratin – the tough, fibrous protein important for the structure of skin, hair and nails.1  Within our skin, keratin-making cells are present in the upper layers (the epidermis) and travel upwards over time, becoming rough, dry and flaky, and producing a “dead” layer of cells (called the stratum corneum), which acts as a constantly renewing barrier to the outside world. 2  Fortunately, under normal, healthy conditions, this top skin layer is dry and not easily invaded by dermatophytes.

However, the scales can easily be tipped in the favour of fungal growth. Dermatophytes particularly love warm, moist environments, which are often created in our active lifestyles.1 Getting sweaty and hot when playing sports or wearing enclosed footwear can create a haven for dermatophytes to thrive. It is perhaps therefore not surprising that some fungal skin infections are commonly called things like “jock itch” (tinea cruris) and “Athlete’s foot” (tinea pedis)! In addition to our sporting activities and fashion trends, having trauma, metabolic disorders (e.g. diabetes) or weakened immune defence can also create opportunities for fungal infections to take hold.3

When dermatophyte skin infection occurs, fungal spores from the environment that are normally harmlessly attached to the top layers of the skin germinate into tubes called mycelia. 4,5  The dermatophytes reach into the upper, keratin-rich layers of the skin (epidermis) by extending long, branched ropes called hyphae.5,6 Here, they release “Pac-man” like proteases that chomp their way through our keratin, breaking it down for nutrients to live on, and make themselves feel at home.5,7

In some cases, dermatophytes can grow into deeper layers of the skin, and cause more serious infections.3 However, usually the fungi stay in the upper layers of the skin, growing outwards into a ring-shaped rash. As a result, some of these infections have the common name of “ringworm” (tinea corporis), even though the culprit is a dermatophyte rather than a worm!  Whilst not usually serious, this is usually irritating and itchy, highly embarrassing and something we want to get rid of as quickly as possible. Fortunately, current and emerging anti-fungal drugs can help us to evict these unwanted residents. Anti-fungal creams or tablets can provide the medical means to specifically attack fungal cells, whilst leaving our own cells intact, relieving us from the irritation and embarrassment of the mouldy microbes we don’t want under our skin. 8

References

  1. American Family Physician. Dermatophyte Infections. Available from: https://www.aafp.org/afp/2003/0101/p101.html [accessed on 28/02/2020].
  2. Verywell Health. What Cell Turnover Is and How It Relates to Acne Development. Available from: https://www.verywellhealth.com/cell-turnover-15552 [accessed on 28/02/2020].
  3. Rouzard C, Hay R, Chosidow O et al. Journal of Fungi (Basel). Severe Dermatophytosis and Acquired or Innate Immunodeficiency: A Review. 2016; 2(1): 4.
  4. Science Direct. Spore Germination. Available from: https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/spore-germination [accessed on 28/02/2020].
  5. Vermout S, Tabart J, Baldo A et al. Mycopathologia. Pathogeneis of Dermatophytosis. 2008: 166: 267-275
  6. Jensen J-M, Pfeiffer S, Alaki T et al. Journal of Investigative Medicine. Barrier Function, Epidermal Differentiation, and Human β-Defensin 2 Expression in Tinea Corporis. 2007: 127(7): 1720-7.
  7. Kaufman G, Horwitz BA, Duek L et al. Medical Mycology. Infection stages of the dermatophyte pathogen Trichophyton: microscopic characterization and proteolytic enzymes. 2007; 45: 149-155.
  8. Centers for disease control and prevention. Fungal diseases. Available from: https://www.cdc.gov/fungal/diseases/ringworm/treatment.html [Accessed on 11/10/2019]

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Fungal infections

According to official international statistics on the prevalence of in the world, fungal infections have been ranked second among all skin diseases for many years in a row. They not only reduce the quality of life and cause discomfort, but also provoke allergic reactions, chronic inflammatory processes and many other pathologies.

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Due to the peculiarities of their microbiological nature, fungal diseases can be actively transmitted from the carrier to a healthy person, and in addition to the skin, affect the nail plates, hair, internal organs and cause their various pathogenic changes. Some fungi are prone to recurrence, have a fairly long incubation period and very similar external manifestations. At the same time, some types of mycoses are treated only with oral preparations, others with cutaneous forms, therefore it is absolutely impossible to self-medicate and contact specialists at the first symptoms.

When tests for fungal infections are ordered

By external signs, it is only possible to initially diagnose a fungal disease. Therefore, with redness of the skin, focal lesions of the smooth and hairline, as well as itching in the foot or skin folds, changes in the shape and color of the nail plate, dermatologists prescribe laboratory tests. This allows you to correctly diagnose the nosological form, and, therefore, to select the most effective set of therapy, take the necessary measures to localize the infection and minimize possible side effects.

Types of fungal diseases

Microscopic pathogenic fungi in medical practice have a common name – mycosis (Greek mycosis). Today, more than 100 species of parasitic and pathogenic microfungi are classified, and we will single out the main infections that affect adults and children.

Dermatomycosis

Common fungal diseases that affect the skin, nails and hair. The source of infection can be a person or an animal. They manifest themselves with various symptoms, we will only indicate the most common diseases in our geographical area:

  • rubromycosis is a disease caused by the anthropophilic fungus Trichophyton rubrum. Differs in a variety of clinical manifestations and localization of foci on any part of the body, can affect smooth skin, hair follicles and nails;
  • athlete’s foot (epidermophytosis) also affecting the interdigital folds. Very similar to candidal lesion, and sometimes there is a polymycotic infection;
  • favus – a rare form accompanied by severe baldness of the head. Can be transmitted through combs, underwear, and shaving and haircutting tools;
  • microsporia – trichomycosis , the causative agent of which is the microsporum fungus. On smooth skin it appears as red spots of a clear shape with a peripheral roller, and on the scalp – with small scaly foci;
  • trichophytosis (synonymous with ringworm) . Outwardly, it is manifested by pink-red focal lesions of the skin on any part of the body;
  • epidermophytosis of skin folds . Accompanied by itching, redness and peeling.

Keratomycosis

Mycoses predominantly of the stratum corneum. Among them, the most famous are piedra, erythrasma and bran lichen.
Superficial mycoses are often ignored by many ordinary people, because if multi-colored lichen can be primarily identified by yellowish-brown spots covered with pityriasis scales, then erythrasma is often perceived as age-related darkening of the skin. This is due to the fact that the disease progresses slowly and is localized on the inner surface of the thighs, in the inguinal folds and under the mammary glands in women. The dim darkening of the skin affected by erythrasma is covered with small scaly scales, and although the disease almost does not cause itching, it sharply reduces the protective properties of the skin and spoils the appearance of the infected.

Candidiasis

Diseases caused by yeast-like fungi of the genus Candidosis, which includes more than 150 varieties. They are considered the most dangerous and most common, as they are found throughout the world and can be transmitted from people, birds and pets. In this case, in addition to skin manifestations of candidiasis can:

  • affect mucous membranes;
  • penetrate deeply into tissues and organs;
  • cause septic diseases and allergic changes in the body.

Candidiasis can manifest as a localized and widespread rash on the hands and feet, lesions of the nail folds and scalp, in the form of stomatitis, cheilitis and gingivitis. With internal infection, they cause vulvovaginitis, urethritis, pleuropneumonia, endocrites, meningitis and other diseases.

Visceral and systemic mycoses

Fungal lesions of internal organs caused by infection with taxonomic microfungi and accompanied by severe lesions of the skin, visceral (internal) organs, subcutaneous tissue, nervous system, and even the musculoskeletal system. This group includes more than two dozen fungi, among which there are pathogenic and conditionally pathogenic. The most common are actinomycosis, aspergillosis, histoplasmosis, coccidiodiasis, sporotrichosis, chromomycosis and others.
As a rule, deep mycoses are transmitted indirectly and are difficult to diagnose. Some pathogens demonstrate amazing survivability and resistance to drug therapy, high pathogenicity and significant contagiousness, and can lead to disability and death. Most systemic mycoses act as opportunistic infections in patients with hepatitis and AIDS.

Diagnostic methods for fungal infections

The Northwestern Center for Evidence-Based Medicine offers traditional and innovative research methods. We carry out the following analyses:

Microbiological methods

Microscopy is the most affordable and easy way to diagnose. The study is aimed at confirming infection with superficial mycosis, for which biological material is taken from the patient, which is potentially considered infected: scraping of a pathologically altered nail or skin, eyelash, hair. It refers to qualitative analyzes and allows only to establish or refute the fact of infection. The study takes several days: the resulting material is processed (stained) in a certain way and transferred to microscopic examination to identify elements of the fungus (spores, hyphae).
Microscopy allows you to quickly confirm mycosis, but the type of pathogen and its quantitative concentration is established only for yeast-like and mold species. Therefore, it is often supplemented by cultural research (bakposev). The results of microbiological studies must be interpreted by the attending specialist.

ELISA

Enzyme immunoassay is a modern and highly reliable method for the identification of fungi in a patient’s venous blood. It is a qualitative and quantitative method and can be used as a primary diagnosis and act as a confirmatory analysis of superficial and visceral mycoses.

The method is based on the detection and identification of an immunoglobulin protein to a specific pathogen. Antibodies and antigens provide reliable information about infection with aspargillosis, candidiasis, cryptococcus and dimorphic microfungi. The result of the test is interpreted as “positive” (there is infection) or “negative” (no fungal infection). In some cases, the study may give a questionable result, as a rule, this happens if the patient has recently taken antibacterial drugs.

The study takes from 1 to 5 days. If it is required to reveal the dynamics of the disease, ELISA is carried out at intervals of 14 days.

PCR

Highly accurate test method based on polymerase chain reaction and taking no more than 3 days. It can be used to register any fungal pathogens, but has one drawback – directed research. This means that the laboratory must obtain information on the specific microfungal species whose spores and hyphae are to be identified.
Blood, sputum, prostate secretion or urine can be provided for analysis, but in the last three options it is necessary to ensure the maximum purity of the biological material. The most effective and expedient in the complex diagnosis of systemic and visceral forms of fungal diseases. The study gives qualitative and quantitative results that are interpreted only by the attending physician.

Serological method

Classical studies, in which IgG-prepitins, enolase antigens, proteinases and mannoproteins are more often detected. The study is variable and may be based on the agglutination reaction, titration and RSK. They allow you to get information only about the fact of carrying a mycotic infection or testify to a previously transferred fungal disease.
The analysis may be based on the study of blood serum. With extensive serodiagnosis, the detection of a microfungus can also be carried out in other physiological fluids of the patient.

The results are interpreted by the treating specialist. At the same time, the serological method is often used as a control study for subsequent correction of therapy and determining the effectiveness of treatment.

Risk groups and prevention of fungal infections

Fungal pathogens in a minimal amount are found on the skin of any person. But the uncontrolled use of medicines, especially hormones and antibiotics, can provoke their active growth and subsequent lesions. It should also be noted that deep mycotic infections can enter the body through open wounds. Compliance with the sanitary rules for the treatment of any injuries associated with a violation of the skin minimizes the risks of disease with systemic and visceral microfungi.

High humidity and a constant positive temperature are an ideal environment for the life and reproduction of microscopic fungi. Accordingly, the risk group a priori includes employees and visitors to swimming pools, fitness clubs, bath complexes, spas, as well as employees of laundries and catering establishments.

People with a weakened immune system, a depressed nervous system, a tendency to allergies, a critical underweight and metabolic disorders are also prone to fungal infections. Therefore, the most effective prevention is to strengthen the immune system, impeccable observance of the rules of personal hygiene and systematic examinations by a therapist and a dermatologist.

Cost of services in JSC “NWDM”

The well-coordinated work of all employees and structural divisions of the center, in combination with the rational organization of laboratory and functional studies, allows us to form favorable competitive prices for all types of services. At the same time, the Northwestern Center for Evidence-Based Medicine has state-of-the-art equipment and uses a unique biological material coding system, which makes it possible to accurately identify pathogens of fungal diseases and conduct all studies promptly and strictly confidentially.

Where to get tested for fungal diseases

JSC “SZTSDM” is a modern enterprise with a developed structure of branches and terminals.