INTRODUCTION:

Among the most common disorders in dermatology, fungal infections affect an astounding one billion people globally. Fungal infections of the epidermis and adnexa are known as dermophytosis and cutaneous candidiasis, while fungal infections of the dermis and subcutaneous tissues are known as implantation mycoses.^1,2

Skin lesions can be a symptom of systemic diseases related to invasivefungal infections. Invasive fungal infections and implantation mycoses can result in considerable morbidity and mortality, whereas superficial fungal infections are easily treated. A skin biopsy is typically required to confirm the diagnosis and identify the causative organisms in implantation mycoses and invasive fungal infections with skin involvement due to their various cutaneous presentations. Because fungal infections cause non-specific skin signs, diagnosing them is still difficult. The challenge of cultivating fungal cultures and their recent increase in frequency. The increasing frequency of these diseases highlights the need for dermatologists and general practitioners to possess a thorough awareness of the symptoms and efficient therapeutic techniques. Even though a few studies have compiled case studies from the first ten years of the twenty-first century, there is still a dearth of research, especially in tropical regions, to fully characterize the recent rise in deep fungal infections in Asia. Anthropophilic and zoophilic dermatophytes belonging to the genera Trichophyton (T.), Microsporum (M.), and Epidermophyton (E.) are the main culprits behind skin diseases.^3,4

Some Smart Nanocarrier used in the treatment of Mycosis: Nano-technology-based topical drug delivery methods are quite attractive. Topical medicines don't have the hepatic first-pass effect, are easy to administer, and are frequently well-accepted by patients. Topical medicine may be more advantageous for skin problems because of its decreased potential for systemic negative effects. Nanostructured drug delivery devices can be used to compartmentalize drugs into limited settings, altering the release profile while preserving the drug concentration at the site of action and/or absorption.^5,6 Some important nanocarriers which play an effective role in the treatment of Mycosisas shown in Figure.1

Figure 1: Novel Nano carriers used as a Targeted drug delivery in mycosis

Nanoparticles:

Nanoparticles, small, macromolecular particles ranging from 10 to 1,000nm, can enhance drug activation by protecting it from degradation, improving transport and dissemination, and delaying release. They can also alter the plasma half-life of entangled sedate. Nanoparticles can be applied in various ways, such as topical nanoparticle medical conveyance, which adheres to surfaces and cells to prevent water dissipation. This approach could improve topical medication delivery systems. Nanoparticles offer advantages over conventional colloidal frameworks, such as physical stability, drug security, controlled discharge, biocompatibility, reduced photochemical or oxidative damage, specific targeting, solvent evasion, and large-scale generation flexibility.^5,7,8

Liposomes:

It is a spherical lipid-based vesicular structure made of two hydrophilic layers atop a lipophilic bilayer. A liposome can be used to deliver genes, tiny chemicals, peptides, and monoclonal antibodies due to its versatility and advantages. Among the many nanomedicines out there, liposomes have helped people with cancer, diabetes, neurological diseases, cardiovascular diseases, and inflammation.^9,10 In addition to their importance in many different aspects of health, parenteral administration gives medications a targeted delivery, so they're less likely to cause side effects and more bioavailable. It also avoids gastrointestinal side effects, low gastrointestinal permeability, and first-pass metabolism issues that can happen with oral medications.^11,12

Niosomes:

Niosomes are microscopic lamellar structures made of cholesterol and non-ionic surfactants, with an amphiphillic bilayer structure for collecting hydrophilic drugs and entrapping hydrophobic drugs within the bilayer. Scientists have hydrated a cholesterol-based combination with a single-alkyl chain nonionic surfactant to create a vesicular system, forming niosomes from various nonionic surfactant classes including polyglycerol alkyl ethers, crown ethers, ester-linked surfactants, glucosyldialkyl ethers, polyoxyethylene alkyl ethers, Tweens, and spans, renowned for their nontoxicity, lack of charge, and ease of use.^13,14

Transferosomes:

Transferosomes, flexible vesicles invented in the early 1990s, are being studied for their potential in transdermal delivery (TDD). These artificial carriers mimic cell vesicles or exocytosin cells, making them suitable for targeted drug administration. They have malleable membranes, self-regulating membranes, and hydrophobic and hydrophilic moieties, allowing them to retain pharmaceutical compounds with varying solubilities. They pass through pores without noticeable loss.^15,16,17

Ethosomes:

Traditional liposomes called ethosomes have a high alcohol concentration, which causes them to have deeper skin penetration and systemic circulation. Highly lipophilic medications can become more soluble and have better permeability when ethosomes have higher ethanol contents. Ethanol causes disruptions to the intercellular lipid structure of the stratum corneum because it contains phospholipids. The topical administration approach of econazole nitrate ethosomal gel was discovered to offer outstanding promise due to its regulated drug release, increased antifungal activity, and superior storage stability. The newly developed novel delivery system demonstrated enhanced anti-fungal activity when compared to other delivery systems when the clinical effectiveness of fluconazole-encapsulated ethosomes in a suitable dermatological base for the treatment of candidiasis was compared to the drug's hydroethanolic solution and liposomal gel marketed products.⁵ It was discovered that the newly developed novel delivery system showed enhanced anti-fungal activity compared to other delivery systems.^5,18,19

Transethosomes:

Transethosomes (TEs) are incredibly malleable vesicles that have the ability to safely transfer medications through the skin. They consist of phospholipids, ethanol, and a permeation enhancer or edge activator. The phospholipids' type and concentration have an impact on the vesicles' size, Zeta potential, and entrapment effectiveness. TEs can administer both synthetic and natural drugs.^7,20

Cubosomes:

Cubosomes are nanostructured, submicron particles with a bicontinuous structure. They are used in pharmaceutical and cosmeceutical applications for controlled drug release. Miconazole nitrate-loaded cubosomes showed 100% drug release after 8 hours, with enhanced antimycotic effectiveness against Candida albicans. Cubosomes are based on lipids and self-assemble to form a cubic lattice. Nonionic surfactants like monoolein are commonly used to construct these nanoparticles.^21,22,23,24

Ufasomes:

UFAsomes are restricted to the pH range of 7 to 9, and are suspensions of closed lipid bilayers made up of fatty acids and their ionized species (soap). In UFAsomes, fatty acid molecules are arranged with their hydrocarbon tails pointing in the direction of the membrane's interior and their carboxyl groups in contact with water. Stable UFAsome formulation has several important elements, including the right choice of fatty acids, buffer, pH range, cholesterol level, lipoxygenase amount, and presence of divalent cations. Recent developments provide the opportunity to design UFasomes with tunable properties such as greater stability, a greater pH range, and resistance to divalent cations. Additionally, the potential use of fatty acid vesicles, or UFasomes, in the topical administration of clotrimazole has been studied. Oleic acid vesicles are made using a thin film hydration process.^5,25

Nanoemulsion:

Nanoemulsions, sometimes known as mini-emulsions or sub-micron emulsions (SMEs). These emulsions are made up of water and oil, and the average droplet size is between 100 and 500nm. They are very stable and do not undergo phase separation in storage.^26,27 They are appropriate for the transfer of lipophilic substances because of their liquid lipophilic core. Several studies have shown that decreased trans epidermal water loss is supportive of the skin's barrier function. Notably, because nanoemulsions have such a low viscosity, they can be sprayed.^28,29,30

Microemulsion:

Microemulsions, transparent combinations of surfactants, water, and oil, are thermodynamically stable and optically isotropic. They are dynamic systems with dynamic interfaces, good cutaneous and transdermal transport properties, and biodispensibility. They can adapt to changing skin and hair conditions due to their high lipid content and restructuring activity.^26,31

Micelles:

Micelle, a nanoscale colloidal medicinal carrier, enhances bioavailability of water-insoluble medications by attaching pH-, thermo-, ultrasound-, or light-sensitive block copolymers to specific ligands. New block copolymers like MPEG-hexPLA have been studied for their impact on miceller carriers loaded with econazole nitrate. In-vitro skin transport experiments showed higher drug deposition in swine skin than commercial liposomal formulations, suggesting the use of micellar solutions of amphiphiles for drug delivery.^33,34 Micelle cores provide a hydrophobic environment, allowing water-insoluble drugs to be easily dissolved and delivered to the intended sites. This reduces drug loss and degradation, avoids adverse effects, increases bioavailability, and raises pharmaceutical concentration.^35,36 Common drug carriers include cells, cell ghosts, lipoproteins, liposomes, soluble polymers, and amphiphilic polymers.³⁷ However, low molecular weight surfactants often cause thermodynamic and kinetic instability in their micelles, leading to turbid dispersions.^38,39,40

Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs):

Nanoparticulate carrier systems like solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are increasingly used for treating fungal infections related to the skin. These carriers, due to their nano size, can make close contact with the stratum corneum, enhancing drug penetration. They also show reduced toxicity and provide regulated release characteristics for various substances. Recently, nanostructured lipid carriers (NLCs) have been produced and loaded with antifungal drugs, resulting in increased drug accumulation in the skin. A study on immune suppressed albino rats confirmed the maximum therapeutic efficacy of NLCs, confirming their potential for topical delivery and effective treatment of potentially fatal cutaneous fungal infections.^41,42

Metal Nanoparticles:

Metal nanoparticles, ranging from 10-100nm in size, are gaining popularity due to their unique structural and functional properties. These clusters of metal atoms have distinct optical qualities, with gold showing reddish-ruby colors and 100-200nm ones blue. Their high aspect ratio allows for accelerated diffusion even under critical temperatures. Localized surface plasmon resonance gives these nanoparticles their optical effects, making them useful for applications like plasma absorption, biological imaging, and surface-enhanced Raman spectroscopy. However, they also have drawbacks like pollution, binding difficulties, molecular instability, and biological harmfulness. Ideal preparation involves a reproducible, accessible, and cost-effective method for size-controlling reagents.^43,44,45

Nanosponges:

Nanosponges are porous polymeric delivery devices that passively focus cosmetic chemicals onto the skin, reducing total dosage and blocking systemic absorption. A feasibility study using ethyl cellulose, polyvinyl alcohol, and econazole nitrate was conducted. Carbopol 934 NF was used as the polymer and permeation enhancers were added to the nanosponges. The study found econazole nitrate stable in the nanosponge delivery system.^46,47

Silver Nanoparticles:

Silver nanoparticles are widely used in cosmetic product formulations due to their stability, UV protection, sensory benefits, and antifungal and antibacterial properties, but further research is needed due to potential harm.⁴⁸

Gold Nanoparticles:

Gold nanoparticles are highly regarded due to their unique chemical and physical properties, making them ideal for various biological applications, including topical medication delivery, although cost remains a significant challenge.^5,49

Nano Fibers:

Nanofibers are materials with a diameter under one micrometer and a high surface area to volume ratio. They have potential applications in water/air filtering, vehicles, textiles, medical devices, biosensors, electronics, and energy storage solutions.⁵⁰ Polymeric nanofibers have been studied for their potential use in biopharmaceutical delivery due to their properties. Cetylpyridinium chloride nanofibers have been developed as an efficient and safe antifungal agent, showing significant improvements over previous dosage forms. Researchers developed a controlled drug delivery system using polyvinyl pyrollidine to enhance bioavailability. The drug's antifungal effect in nanofibers was confirmed, with clotrimazole (CZ)-loaded microemulsion showing the highest drug release, cytotoxicity, antifungal activity, and entrapment efficiency. Fluconazole nanofibers showed continuous drug release for six hours. Studies on antibacterial activity have shown that drug-loaded polymeric nanofibers have better antimicrobial action against Candida albicans compared to ordinary medication.^5,51

Dendrimers:

Dendrimers represent newly engineered polymeric systems that possess enhanced chemical and physical characteristics due to their unique three-dimensional forms. Their macrodispersity, molecular weight, dimensions, and geometry are well-defined. Through modifications to their terminal groups, dendrimers can be tailored for targeted drug delivery and are compatible with coupling to drug compounds and biologically active molecules like DNA, heparin, and various polyanions. They are also capable of encapsulating hydrophobic and hydrophilic drugs within their dendrimer frameworks, imparting miscibility, reactivity, and solubility. PEGylation, the attachment of PEG polymers, has been shown to neutralize the inherent cationic charge of some dendrimers which mitigates their toxicity. Published evidence suggests dendrimers may serve as effective carriers for antifungal therapeutics. Additionally, these polymers warrant further exploration for fundamental drug delivery applications as well as formulating semi-solid antimicrobial dosage forms containing dendrimer structures.^5,52,53 A dendrimer can be used for drug targeting as well as solubility augmentation. We anticipated that dendrimers might be employed as excipients with many uses. Researchers are investigating dendrimers for their capacity to achieve multiple goals within a single formula, including enhancing drug solubility, dissolution rate, gastrointestinal absorption, bioavailability, stability, multi-drug encapsulation, regulated release, and therapeutic efficacy.^54,55

CONCLUSION:

Nanocarriers offer numerous advantages over conventional drug delivery systems, including improved therapeutic efficacy and reduced drug release complications due to their rapid release capabilities. Nanocarriers can stabilize drugs from degradation, lower dosing, and accelerate healing by controlling drug release. They can improve drug solubility, permeability, and bioavailability, which may be challenging to target at the disease site. NPs, known for their flexibility, controlled size, optimal drug release, biocompatibility, and response to fungal infections like mycosis, skin allergy etc. have been acknowledged and it has been used in an intensive form of applications. Advancements in nanocarrier surface modification have enabled unique binding with ligands and drug release at the target site, demonstrating continuous progress. The advancement of techniques and extensive advancements in the field of Nanocarriers are being combined for advanced understanding. Commercial products show significant results in vivo, predicting the efficacy and safety of nanocarriers in treating ailments like fungal infections, skin allergy cancer, wounds etc.

ACKNOWLEDGEMENT:

All authors are highly thankful to Agra Public College of Higher Education and Research Center, Artoni Agra for provided technical support for article writing.

CONFLICT OF INTEREST:

All authors declare no conflict of interest.

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Received on 07.03.2024 Modified on 30.03.2024

Res. J. Pharma. Dosage Forms and Tech.2024; 16(2):151-156.

DOI: 10.52711/0975-4377.2024.00024