Add Sugar to Chitosan: Mucoadhesion and In Vitro Intestinal Permeability of Mannosylated Chitosan Nanocarriers

Crosslinked chitosan nanocarriers (140-160 nm) entrapping coumarin-6 (lambda(ex/em) = 455/508 nm) with or without surface mannosylation were synthesized and assessed for cytotoxicity, adherence and cellular uptake in Caco-2 cells, flux across Caco-2 monolayers, and mucoadhesion to porcine mucin. Mannosylated and non-mannosylated nanocarriers demonstrated biocompatibility with slow release of coumarin-6 at pH 6.8 and 7.4 over 24 h. Adherence of the non-mannosylated nanocarriers (50 and 150 mu g /mL) to Caco-2 cells was similar to 10% over 24 h, whereas cellular uptake of 25-30% was noted at 4 h. The mannosylated nanocarriers showed a similar adherence to non-mannosylated nanocarriers after 24 h, but a lower cellular uptake (similar to 20%) at 1 h, comparable uptake at 4 h, and a higher uptake (similar to 25-30%)t at 24 h. Overall, the nanocarriers did not affect the integrity of Caco-2 monolayers. Mannosylated nanocarriers elicited higher P-app of 1.6 x 10(-6 )cm/s (50 mu g/mL) and 1.2 x 10(-6 )(150 mu g/mL) than the non-mannosylated ones: 9.8 x 10(-7 )cm/s (50 mu g/mL) and 1.0 x 10(-6) (150 mu g/mL) after 2 h. Non-mannosylated chitosan nanocarriers elicited enhanced adhesion to porcine gut mucin via mucin-filled microchannels due to higher cationic charge density. These results underpin the importance of surface chemistry in the biological interactions of nanocarriers, while highlighting the role of surface hydrophilicity in mucopermeation due to mannosylation.