**2.2 Influence of NPs shape and aspect ratio on GIT toxicity**

It was reported that the shape of NPs can impact their association with the GIT as well. NPs with round shapes have been discovered to exhibit a higher level of interaction with the mucous layer compared to alternative forms, such as cylindrical or cubic shapes [61]. This occurs because round NPs possess a larger surface area-to-volume ratio, which can increase their connection with the mucous layer [4]. In addition to size, the configuration and proportion of NPs are essential factors in determining their cytotoxic effects *in vivo* [64]. Vedhanayagam et al. [65] investigated the impact of various zinc oxide NPs, such as spheres, needle, rod, hexagonal, star, flower, doughnut, circular discs, and cube, on the healing process of wounds. The researchers found that the spherical structure of zinc dioxide (ZnO) within a cross-linked collagen framework leads to improved re-epithelization and more rapid collagen accumulation. A higher aspect ratio of NPs is believed to be linked to increased cytotoxicity due to decreased clearance and enhanced bioavailability of these particles [66]. NPs with higher aspect ratios often exhibit cytotoxicity patterns that resemble those of asbestos. These particles can cause macrophage cell death during phagocytosis and, similar to asbestos fibres, can contribute to cancer formation [67].

### **2.3 Influence of NPs charge on GIT toxicity**

NPs with positive charges have been shown to have a stronger connection with the negatively charged mucous layer compared to those with a negative charge or no charge at all. Researchers have explored using charged polymers to temporarily open tight junctions and enhance drug delivery across the intestinal epithelial barrier. For example, chitosan (a cationic polymer) has been shown to promote the paracellular transport of NPs [68]. NPs' bioavailability and absorption have been studied only a few times after oral administration with regard to surface charge, hydrophobicity, and shape. NPs with a positive charge demonstrated increased absorption and movement by enterocytes compared to those with a negative or neutral charge, as well as a notable increase in oral bioavailability *in vivo* [69]. Furthermore, rod-shaped gold NPs (AuNPs) and DNA struggle to permeate or enter cells because of their charge. To enhance uptake, both AuNPs and DNA have undergone surface modification by adding lipid layers, while DNA has also been electrostatically attached to cationic liposomes, facilitating transport into cells [21].

*Potential Toxicity of Nanoparticles for the Oral Delivery of Therapeutics DOI: http://dx.doi.org/10.5772/intechopen.111946*

#### **2.4 Influence of NPs surface chemistry on GIT toxicity**

Numerous NPs undergo modifications to alter their surface chemistry for specific objectives [70]. For instance, applying a polyethylene glycol (PEG) coating on NPs surfaces to establish water-attracting surface chemistry lessened the intense interaction with mucus components and increased particle movement across the mucus and mucosa [69]. Furthermore, Hasse and colleagues reported that peptide-coated silver NPs (20 nm) were more cytotoxic than citrate-coated silver NPs of the same size. They evaluated cytotoxicity in a human leukaemia cell line using the WST-1 assay [71]. It was perceived that the toxic effects of AgHECp (Silver hexagonal close placed), Ag pristine, and AgPVP (silver polyvinylpyrrolidone) were examined in A431 cell lines (human epidermoid carcinoma) and HaCaT (human keratinocytes) cell lines [71]. It has been revealed that smaller particles with negative surface charge and increased ionic content, such as AgPVP, were highly toxic. Similarly, toxic effects were observed for the larger particles, which were pure AgNP with a negative surface charge and ion content comparable to AgPVP [71]. Additionally, NPs featuring a hydrophobic surface exhibit a more robust interaction with the mucous layer than their hydrophilic counterparts. A cationic polysaccharide with mucoadhesive properties, chitosan has been extensively investigated. Chitosan's mucoadhesive potency is limited due to its low water solubility and low mucoadhesive strength, so it must be chemically modified to optimise its mucoadhesive properties [72].
