Enhanced Mucoadhesion of Thiolated -Cyclodextrin by S-Protection with 2-Mercaptoethanesulfonic Acid

This study aimed at designing an S-protected thiolated beta-cyclodextrin (beta-CD) exhibiting enhanced mucoadhesive properties. The native beta-CD was thiolated with phosphorus pentasulfide resulting in a thiolated beta-CD (beta-CD-SH) and subsequently S-protected with 2-mercaptoethanesulfonate (MESNA) to form beta-CD-SS-MESNA. The structure of the novel excipient was confirmed by H-1 NMR and Fourier-transform infrared spectroscopy. The sulfhydryl content of beta-CD-SH, determined by Ellman's test, was 2281.00 +/- 147 mu mol/g, and it was decreased to 45.93 +/- 19.40 mu mol/g by S-protection. Due to thiolation and S-protection, the viscosity of the mixture of mucus with beta-CD-SH and beta-CD-SS-MESNA increased 1.8 and 4.1-fold, compared to native beta-CD, respectively. The unprotected beta-CD-SH diffused to a lesser extent into the mucus than native beta-CD, while S-protected beta-CD-SS-MESNA showed the highest mucodiffusion among the applied CDs. A 1.5- and 3.0-fold higher cellular uptake of beta-CD-SH and beta-CD-SS-MESNA, compared to the native one, was established on Caco-2 cell line by flow cytometry, respectively, causing slightly decreased cell viability. On account of the enhanced mucoadhesion, this higher cellular uptake does not affect the application potential of beta-CD-SS-MESNA as an oral drug delivery system since the carrier remains in the mucus and does not reach the underlying epithelial layer. According to these results, the S-protection of beta-CD-SH with MESNA promotes improved mucodiffusion, strong mucoadhesion, and prolonged mucosal residence time.