Thiolated Cellulose: A Dual-Acting Mucoadhesive and Permeation-Enhancing Polymer
Gergely Kali, Bengi Özkahraman, Flavia Laffleur, Patrick Knoll, Richard Wibel, Katrin Zöller, Andreas Bernkop‐Schnürch
Abstract
High Resolution Image Download MS PowerPoint Slide This study aims to design an anionic, thiolated cellulose derivative and to evaluate its mucoadhesive and permeation-enhancing properties utilizing enoxaparin as a model drug. 2-Mercaptosuccinic acid-modified cellulose (cellulose–mercaptosuccinate) was synthesized by the reaction of cellulose with S -acetylmercaptosuccinic anhydride. The chemical structure of the target compound was confirmed by FTIR and 1 H NMR spectroscopy. The thiol content was determined by Ellman’s test. The conjugate exhibited 215.5 ± 25 μmol/g of thiol groups and 84 ± 16 μmol/g of disulfide bonds. Because of thiolation, mucoadhesion on porcine intestinal mucosa was 9.6-fold enhanced. The apparent permeability ( P app ) of the model dye Lucifer yellow was up to 2.2-fold improved by 0.5% cellulose–mercaptosuccinate on a Caco-2 cell monolayer. Enoxaparin permeation through rat intestinal mucosa increased 2.4-fold in the presence of 0.5% cellulose–mercaptosuccinate compared with the drug in buffer only. In vivo studies in rats showed an oral bioavailability of 8.98% using cellulose–mercaptosuccinate, which was 12.5-fold higher than that of the aqueous solution of the drug. Results of this study show that the modification of cellulose with 2-mercaptosuccinic acid provides mucoadhesive and permeation-enhancing properties, making this thiolated polymer an attractive excipient for oral drug delivery.