Review on Nanomaterials and Nano-Scaled Systems for Topical and Systemic Delivery of Antifungal Drugs

Figures & data

Figure 1 Virulence attributes of a prototypic human pathogenic fungus in interaction with the host.

Figure 2 Iron homeostasis in Saccharomyces cerevisiae and major human pathogenic fungi.

Figure 3 Schematic representation of the most commonly used nanomedicine types composed of different kinds of materials.

Table 1 Novel Approaches for Antifungal Therapy Summery

Antifungal Agent	Novel Formulations	Benefits
Nystatin	Solid Lipid Nanoparticles	It delivers the active substance to the target organ at therapeutically significant levels. Absorption-increasing effects. Controlled-release properties. Accommodate a high amount of drugs. Negligible side effects.
	Liposomal Gel	Excellent vehicle for topical delivery of drug as it increases the drug permeation.
	Nanoemulsions	Avoiding undesirable side effects Prevent the toxicity of potential systemic absorption of the drug.
	Niosome	Increases the efficacy and safety of nystatin. Use as an alternative to liposomes. Niosomal encapsulation provides means for parenteral administration
	Liposome	Increase efficacy Useful in prophylactic perspectives
Amphotericin B	Nano-emulsions	Cost-effective, non-nephrotoxic, and thermodynamic stability. Nanoemulsion formulation has potentials Antifungal activity than commercial formulations.
	Solid Lipid Nanoparticles	Increase in percent relative bioavailability and half-life in comparison to the plain drug. Provide successful oral administration. Controlled-release property.
	Liposomes	Lower incidence of infusion-related adverse events and nephrotoxicity. It improves the efficacy of the drug.
	In situ Gel	Effectively delivers the drug for an extended duration of time in a controlled-release manner. Improve therapeutic efficacy.
	Niosomes	Sustained release of drug Greatly enhance retention of the drug over the surface.
	Ethosomes	Enhance antifungal activity by enhancing the permeation of the drug.
	Microspheres	High entrapment. Effective drug release for an extended period of time.
	Microemulsions	Provide thermodynamic stability. Enhance drug solubility.
Itraconazole	Microparticles	Increase the rate of drug release. Stable formulation
	Transfersomes	High entrapment efficiency. Enhance permeation. Sustained drug release
	Buccal adhesive in-situ gel	Better bioavailability Longer residence time over the applied surface. Controlled release of the drug.
	Mucoadhesive Tablets	Sustain the drug release. Improved oral bioavailability. Enhanced the dissolution rate of itraconazole
	Solid lipid nanoparticles	Improve therapeutic efficacy. Reduction of toxicity of this broad-spectrum antifungal agent. Targeting potential.
	Gastroretensive tablets	Increase mean residence time of tablet in gastrointestinal tract. Enhance the solubility of the drug. Controlled release of drugs for a prolonged period of time
	Niosomes	Increases permeation compared to the itraconazole solution. Stable formulation.
	Nanosuspension	Increases the aqueous solubility of itraconazole. Higher drug release. Increase oral absorption of the drug
Clotrimazole	Polymeric Nanoparticles	Significantly higher anti-fungal activity then conventional formulations.
	Solid lipid nanoparticles	Prolonged-release of the drug. Successfully localize the drug in the skin to treat topical fungal infections.
	Nanofibres	Release drugs in a predetermined way for a prolonged period of time. Reduce the frequency of drug administration.
	Mucoadhesive tablets	Increase its solubility by complexation with β‐cyclodextrin. Improve the bioavailability of drugs through the buccal mucosa.
	In-situ Gels	Control drug release and protect the medicaments from a hostile environment. Represent sustained-release behavior.

Table 2 Summary of Challenges in Translation of Nanoparticles in Stage of Development and Different Steps in the Clinical Trial

Stage of Development and Different Steps in the Clinical Translation of Nanoparticles	Challenges
Synthesis	✓ Extreme temperature and solvent incompatibility for low-cost polydimethylsiloxane micro channels ✓ Higher costs and complexities in the fabrication of glass and silicon
Characterization	✓ Current methods are not applicable to all classes of nanoparticles ✓ Not all properties can be characterized, such as drug encapsulation and release, and signal-to-noise ratio
In vitro	✓ Higher costs and complexities in the fabrication and operation compared with well plates ✓ Might not be reusable and if reusable, it would be difficult to keep sterile
In vivo	✓ Lack of methods to translate data from small-scale organisms to other species ✓ Pharmacokinetics or biodistribution cannot be determined
Large-scale synthesis	✓ Difficult to build systems at low-cost that are comparable to a batch reactor able to prepare grams or kilograms of nanoparticles