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

interaction of NPs. The GIT represents a selective mucosal barrier, with an estimated surface area of 200 m2 in adult humans, that can potentially interact with ingested NPs [27]. The anatomical and physiological characteristics of each part of the GIT can affect NPs absorption and elimination [28]. For example, the stomach presents a tough barrier to drug absorption, with a strong acid environment (pH range of 1.0–2.5) that can degrade food, acid-labile drugs, and pathogenic microorganisms. Furthermore, the stomach has extrinsic epithelial cells and a mucin-bicarbonate barrier, which, combined with tight junctions beneath the intrinsic barrier, limits drug absorption. Furthermore, stomach pepsins can inactivate protein drugs [13]. The small intestine has a huge surface area due to the villi and microvilli in the intestinal lumen [29]. The small intestine is considered a major site for oral drug delivery due to its enormous surface and various transport routes [13]. The intestinal mucosa can recognise and transfer ectogenic antigens to the immune system. However, some challenges to drug delivery in the small intestine still arise from its unique physiology [30]. DDS that can increase their retention time in villi and microvilli, improve lipid solubility, and interact with a specific receptor or carrier can increase their overall bioavailability [13, 31]. Therefore, the unique anatomical and physiological features of each part of the GIT play a crucial role in the interaction and potential toxicity of NPs in the GIT.

The interaction of NPs with GIT depends on their physicochemical properties, including size, shape, surface charge, and surface chemistry (**Table 1**) [58]. Following oral administration, NPs encounter the mucous layer covering the GIT, which


**Table 1.**

*Some studies on the toxic effects of various nanoparticles on different models.*

protects against harmful agents, such as pathogens and toxins [59]. However, NPs can interact with the mucous layer and penetrate the underlying tissue, resulting in potential toxicity [60].

### **2.1 Influence of NPs size on GIT toxicity**

Smaller NPs possess a higher surface area-to-volume ratio, promoting better engagement with the mucous layer and increased absorption into the tissue [61]. Conversely, larger NPs may interact less with the mucous layer and could be eliminated from the GIT before reaching the tissue. Zhao et al. [62] noted that a 100 nm nano-vaccine showed superior pharmacokinetic effectiveness compared to a 500 nm nano-vaccine when an alum adjuvant was administered. The toxicities of NPs are inversely proportional to their size, and they are generally more toxic than large particles of the same chemical substance [63].
