Table 1.

Key design criteria to consider for GIT-targeted oral NPs.

	Oral vaccine	Oral tolerance	Modulation of lamina propria immune cells	Intestinal barrier enhancement	Modulation of gut microbiota
Harsh GIT conditions (pH variation, proteolytic enzymes)	Should consider (antigens should be protected by NPs encapsulation)		Could consider when loaded drugs or targeting ligands are vulnerable (drugs should be protected by NPs encapsulation, and targeting ligands should be protected, for example by embedding NPs in hydrogels)
Short residence time in small intestine	Should consider (antigens should be delivered to APCs in the inductive sites of small intestines)		Should consider if targeting the small intestine
Penetration through the intestinal barrier (mucus layer, epithelium)	Should consider (Both M-cells and epithelium are located underneath the epithelium)		Should consider (The lamina propria is located underneath the epithelium) when the intestinal barrier structure is intact	Should consider penetrating through the mucus layer for epithelium targeting when the intestinal barrier structure is intact
			Not applicable for certain diseases such as IBD with denuded mucus layer and disrupted intestinal epithelium
Targeting strategy	- M-cell targeting - Epithelium targeting	- M-cell targeting - CD103+ DC targeting	- Targeting innate immune cells (e.g., macrophages, neutrophils, Ly6C+ mononuclear phagocytes)	- Mucus targeting - Epithelium targeting	- Mucus targeting - Large intestine lumen targeting
Other considerations	- Should consider using immunostimulatory adjuvants	- Should consider using immunomodulatory agents