Enhanced water-solubility and mucoadhesion of N,N,N-trimethyl-N-gluconate-N-homocysteine thiolactone chitosan

• TM-GN-HT-chitosan is an improved water-soluble mucoadhesive chitosan.
• TM-GN-HT-chitosan is markedly more soluble than chitosan at all pH.
• TM-GN-HT-chitosan is soluble over a wide pH range (pH 2–11).
• Mucoadhesiveness of TM-GN-HT-chitosan is 5.0- to 9.5-fold higher than chitosan at pH 1.2–6.4.

A water-soluble chitosan with improved mucoadhesion was prepared by modifying 19.4% of the amine groups of chitosan to trimethylammonium and conjugation of gluconolactone (GLU) and homocysteine thiolactone (HT) onto the remaining amine groups of the chitosan backbone. The derived trimethyl-gluconate-HT-chitosan (TM-GN-HT-chitosan) was confirmed by Fourier Transform Infrared spectroscopy, NMR and thermogravimetric analysis. The total thiol and disulfide group level on the TM-GN-HT-chitosan were17.96 ± 0.03 and 7.36 ± 0.03 μmol/g, respectively. The water solubility of the TM-GN-HT-chitosan conjugate was 79.0 ± 0.15%, more than that of TM-chitosan and chitosan, with an enhanced solubility over a broad pH range ranging from 85.6 ± 10.4% to 58.5 ± 1.1% maximal solubility at pH 2 to 11. Finally, TM-GN-HT-chitosan showed a nearly ∼9.5-, 5.0- and 5.6-fold higher mucoadhesiveness than chitosan at pH 1.2, 4.0 and 6.4, respectively, and was optimal at pH 4.0.