Mucoadhesive nanoparticles made of thiolated quaternary chitosan crosslinked with hyaluronan

► Thiolated quaternary chitosans were obtained from a chitosan of 32kDa MW. ► Nanoparticles were obtained by interaction of these polymers with hyaluronan. ► The nanoparticles were modispersed and showed mucoadhesivity. ► The nanoparticles were internalized by endothelial progenitor cells. ► The nanoparticles improved cell resistance to oxidation. Mucoadhesive polymeric nanoparticles intended for drug transport across the gastrointestinal mucosa were prepared from quaternary ammonium–chitosan conjugates synthesised from reduced-MW chitosan (32kDa). Conjugates contained pendant moieties of 2–4 adjacent diethyl-dimethylene-ammonium groups substituted on repeating units (26–55%). Conjugates were thiolated via amide bonds with thioglycolic acid to yield products with thiol content in the 35–87μmol/g range. Nanoparticles with mean size in the 270–370nm range and positive zeta-potential (+3.7 to +12.5mV) resulted from ionotropic gelation of the thiolated conjugates with de-polymerised hyaluronic acid (470kDa). The nanoparticles were fairly stable in size and thiol content and showed a significant mucoadhesivity, matching and even exceeding that of the constituent polymers. Nanoparticles were internalised by endothelial progenitor cells in direct relation to their surface charge intensity. Nanoparticle uptake significantly improved cell viability and resistance to oxidation. The lyophilised nanoparticles were re-dispersible and could make a manageable formulation for oral use.