Novel thiolated carboxymethyl chitosan-g-β-cyclodextrin as mucoadhesive hydrophobic drug delivery carriers

A novel thiolated carboxymethyl chitosan-g-β-cyclodextrin (CMC-g-β-CD) drug delivery carrier was synthesized and characterized. Thiolated CMC-g-β-CD was synthesized using two steps. First, carboxymethyl β-cyclodextrin (CM β-CD) was grafted onto carboxymethyl chitosan (CMC) using water-soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as the condensing agents. Next, the resultant product was further grafted with cysteine methyl ester hydrochloride (CMEH). Its structure was confirmed by FT-IR and 1H NMR spectral analysis. X-ray diffraction (XRD) analysis on the resulting product showed that the peaks at 2θ = 10° and 20° decreased greatly in thiolated polymers, indicating that these polymers are more amorphous in nature. The swelling study showed that the water uptake of thiolated CMC-g-β-CD was higher than that of the unmodified chitosan control. The adhesive properties of thiolated CMC-g-β-CD were evaluated in vitro on a freshly excised mouse mucosa, and a fivefold increase in the adhesion time was found in thiolated CMC-g-β-CD when compared with the unmodified chitosan control. The drug release profile showed that thiolated CMC-g-β-CD tablets provided a slower release of the entrapped hydrophobic model drug, ketoprofen, than the chitosan control, and the release behavior was influenced by the amounts of thiol groups present on the polymer chains. These results suggest that thiolated CMC-g-β-CD with improved mucoadhesive properties may potentially become an effective hydrophobic drug delivery system with controlled drug release capability.