# Nanoarchitectures in Management of Fungal Diseases: An Overview
## 5 Toxicological Overview  
While the number of NPs types and applications continues to increase, studies to characterize their effects after exposure and to address their potential toxicity are few in comparison. Compared to conventional substances in a microscale, NPs (diameter \(<\) 100 nm) stand on a huge reactive surface able to interact with biological systems and cause toxic effects. Most of the antifungal drugs have poor water solubility, which tends to show a lower absorption and bioavailability. It can be improved by forming complexes using nanocarriers. By virtue of their nano sizes, they have greater interactions with biological surfaces, with pro and con effects [102]. Schematic mechanisms of cytotoxic activity of antifungal drug-loaded nanocarriers are represented in Figure 3.  
The cytotoxicity of chitosan NPs (ChNPs) in terms of the percentage of viable cells and percentage of cytotoxicity after their respective treatments has been analyzed. At a dose of 300 mg/mL, ChNPs killed 74.16% of the cell after 24-h incubation. The LD\({}_{50}\) value was obtained as 64.21 mg/mL. The inhibition rate profile of ChNPs indicated that the inhibition of cell viability was found to be dose-dependent [56].  
Spanlastics are nanosized and elastic. Both developed formulations, and the corresponding empty vesicles have not shown any significant toxic effect on the cell proliferation of HGF compared to the control (\(p<0.05\)) at 1% and 5% KTZ in the cell culture suspension medium. There was higher cell viability in the case of blank and drug-loaded vesicles than free drug suspension. Hence, it may be concluded that vesicles do not contribute to cell cytotoxicity [50].  
Different generations of the PAMAM dendrimer are used to enhance the solubility of AmB, whose clinical use is restricted due to poor solubility and nephrotoxicity [103,104]. For topical DDS, dendrimers might be advantageous for quick results of topical irritation. Currently, there are no such studies that can clarify the cationic toxicity of topical dendrimers. The lower groups of cationic dendrimers have exhibited better penetration than the advanced ones [105, 106, 107].  
In a recent study, AgNPs were synthesized using different polymer/protein mixtures, such as \(\kappa\)-carrageenan-hydrolyzed collagen (AgNPColCarr), cashew gum-hydrolyzed collagen (AgNPColCashew), and agar-hydrolyzed collagen (AgNPColAgar) and showed 2.0- and 6.5-fold less cytotoxicity than AgNPCol, respectively. AgNPColCarr demonstrated a MIC value of 62.5 and 31.25 \(\upmu\)m/mL against _E. coli_ and _P. aeruginosa_, respectively. The MOA of AgNPs against yeasts may be related to the generation of free radicals that lead to apoptosis [108].  
In a study, [PERSON] et al. tested the toxicity of empty ultra-deformable liposomes (UDL). The formulations F3 and F4 did not reduce the mitochondrial activity of Keratinocyte (HaCaT) and J774 cells; nonetheless, F4 produced 30% lactate dehydrogenase (LDH) leakage in HaCaT cells at 2.9 mg/mL SPC. The membrane damage was more pronounced on phagocytic (J774) than on nonphagocytic cells (HaCaT) [109].  
Figure 3: Schematic mechanisms of cytotoxic activity of antifungal drug-loaded nanocarriers.