Enhanced Mucoadhesion of Thiolated β-Cyclodextrin by S-Protection with 2-Mercaptoethanesulfonic Acid
Gergely Kali, Ali Magdi Mahmoud Mahmoud Taha, Emiliano Campanella, Martyna Truszkowska, Soheil Haddadzadegan, Nunzio Denora, Andreas Bernkop‐Schnürch
Abstract
High Resolution Image Download MS PowerPoint Slide This study aimed at designing an S-protected thiolated β-cyclodextrin (β-CD) exhibiting enhanced mucoadhesive properties. The native β-CD was thiolated with phosphorus pentasulfide resulting in a thiolated β-CD (β-CD-SH) and subsequently S-protected with 2-mercaptoethanesulfonate (MESNA) to form β-CD-SS-MESNA. The structure of the novel excipient was confirmed by 1 H NMR and Fourier-transform infrared spectroscopy. The sulfhydryl content of β-CD-SH, determined by Ellman’s test, was 2281.00 ± 147 μmol/g, and it was decreased to 45.93 ± 19.40 μmol/g by S-protection. Due to thiolation and S-protection, the viscosity of the mixture of mucus with β-CD-SH and β-CD-SS-MESNA increased 1.8 and 4.1-fold, compared to native β-CD, respectively. The unprotected β-CD-SH diffused to a lesser extent into the mucus than native β-CD, while S-protected β-CD-SS-MESNA showed the highest mucodiffusion among the applied CDs. A 1.5- and 3.0-fold higher cellular uptake of β-CD-SH and β-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 β-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 β-CD-SH with MESNA promotes improved mucodiffusion, strong mucoadhesion, and prolonged mucosal residence time.