LAUSR

&NA; In this study, we synthesised thiolated silica nanoparticles using 3‐mercaptopropyltrimethoxysilane and functionalised them with either 5 kDa methoxy polyethylene glycol maleimide (PEG) or 5 kDa alkyne‐terminated poly(2‐ethyl‐2‐oxazoline) (POZ). The main objectives of this study are to investigate the effects of pH on the size and &xgr;‐potential of these nanoparticles and evaluate their mucoadhesive properties ex vivo using rat intestinal mucosa. The sizes of thiolated, PEGylated and POZylated silica nanoparticles were 53 ± 1, 68 ± 1 and 59 ± 1 nm, respectively. The size of both thiolated and POZylated nanoparticles significantly increased at pH ≤ 2, whereas no size change was observed at pH 2.5–9 for both these two types of nanoparticles. On the other hand, the size of PEGylated nanoparticles did not change over the studied pH range (1.5–9). Moreover, thiolated nanoparticles were more mucoadhesive in the rat small intestine than both PEGylated and POZylated nanoparticles. After 12 cycles of washing (with a total of 20 mL of phosphate buffer solution pH 6.8), a significantly greater amount of thiolated nanoparticles remained on the intestinal mucosa than FITC‐dextran (non‐mucoadhesive polymer, p < 0.005) and both PEGylated and POZylated nanoparticles (p < 0.05 both). However, both PEGylated and POZylated nanoparticles showed similar retention to FITC‐dextran (p > 0.1 for both). Thus, this study indicates that thiolated nanoparticles are mucoadhesive, whereas PEGylated and POZylated nanoparticles are non‐mucoadhesive in the ex vivo rat intestinal mucosa model. Each of these nanoparticles has potential applications in mucosal drug delivery. Graphical abstract Figure. No caption available.