2.1.1. Organic Synthetic and Natural Polymeric NPs

A diversity of nanoparticles and nanoscale products can be developed from synthetic and natural polymers. These NPs are formed from natural and synthetic materials including saccharides and their derivatives such as chitosan, lipids and other biomolecules. A huge variability in the size of these nanomaterials has been reported, with size dimensions spanning from 0.5 to 100 nm. These nanomaterials have high loading/conjugating capacities and have also been used for the development of hydrogel nanoformulations, particularly for the sugars and their derivatives [17]. Synthetic polymeric NPs can be composed of amphiphilic polymers such as caprolactone or PLGA which form a hydrophobic core that facilitates the transportation of hydrophobic drugs encrusted with a water-soluble coat [19]. These NPs have been used for transportation and delivery of drugs with low water-solubility such as amphotericin [20].

Solid lipid nanoparticles developed from a variety of lipids are upcoming drug delivery vehicles which exhibit great potential for lipophilic anti-cancer drugs. These can be easily combined with other materials to induce improved humoral antibody dependent immunity in the animals [21], besides their role in gene therapy by development of nucleic acid-based conjugates [22,23]. The oral, skin and parental routes of solid lipid NPs application are more effective in drug delivery and are highly absorbed [23].

Another category of polymeric nanoparticles includes the most popular forms called liposomes. These are non-toxic PEGylated NPs which are comprised of a two lipid (bilayer) cover shell having high solubility for fatty (hydrophobic) drugs. The first layer of the liposome is coated with a PEG layer to prevent any immune response towards the particles [17,24]. However, due to their vulnerability to get digested in the alimentary canal leading to loss of function, these nanoformulations are preferentially administered through parental and topical routes. Conjugating liposomes with biologically active antibodies can be useful for cancer cell treatment [23]. Further, liposomal formulations of dead pathogens can be utilized to develop vaccines [25]. The liposomes can also be conjugated with DNA to develop DNA vaccines [17]. Furthermore, the liposomes enable drug delivery and diffusion to targeted cell sites within the organism (Figure 1). Despite these benefits and potentially useful activities, these formulations are prone to changes during storage and also the encapsulated compounds may exhibit rapid destruction of their content on account of oxidation processes [26].

Similar to liposomes are the polymeric micelles with one basic difference from the former type that the latter are formed from exfoliated lipid bilayers and thus exhibit great potential to encapsulate lipophilic drugs. Therefore, micelles are hydrophobic core surrounded by a hydrophilic coat which increases their solubility in water [23].

Nano-cochleates are a specialized category of sub-micron to nanoscale solid particulate lipid-based drug carriers [27] which can be derived by the fusion of liposomes with metal cations and involve spiral rolling of continuous lipid bilayer [28,29]. These carriers can be efficiently loaded with both hydrophobic as well as hydrophilic drugs ensuring higher protection from gastrointestinal degradation of anti-fungal drugs particularly Amphotericin and thus enabling oral administration [30,31].

Synthetic polymeric nanoparticles primarily including dendrimers are derivatives of long-chain branched polymers such as polyamidoamines. Similar to micelle nanoparticles, dendrimers are water-soluble, exhibit high biological activities and possess comparatively a much smaller size than the other polymeric NPs discussed so far [26,32]. These attributes of the dendrimers do not allow stimulation of the immune response after parental administration. Dendrimers can be combined with drugs to improve their efficiency for treatment of a variety of animal disorders [26]. The dendrimer formulations have been successfully used for effective cancer treatments and may showcase multiplexed functions including detection of the tumor cells, entry through the cell membrane, targeted release of the conjugated anticancer drugs in the cytoplasm and finally the destruction and death of

cancerous cells [23]. Dendrimers can also conjugate with the lipids of the cell membranes and this can create wide pores in the membrane that potentiate improved entrance of the drug containing dendrimer nanoparticles for targeted delivery leading to higher cell death rates [26].

#### 2.1.2. Nanoemulsions

These are aqueous mixtures of oil or other hydrophobic components prepared by addition of oil to water overlaid by non-chemical surfactants [1,16,33,34]. The micelle size in the prepared nanoemulsions may vary from 0.5 to >500 nm. Nanoemulsions exhibit significantly high antifungal, bactericidal and virucidal activities. It may be attributed to greater adherence of the oil droplets on the surface of the microbial cells which facilitates the entrance of drugs to the cell [5,17,35].

#### 2.1.3. Inorganic Metal/Non-Metal Nanomaterials

These NPs are the first-choice nanomaterials to be used as nanoantifungals due to their low cost, easy application, eco-friendly characteristics and wide viability [1,5]. They exhibit potential as antifungals [29,36,37], besides the other biomedical benefits [24]. These nanomaterials may have individual particle size dimensions ranging from 1 to 100 nm with aggregate sizes have a higher size range.
