Kali, GergelyÖzkahraman, BengiLaffleur, FlaviaKnoll, PatrickWibel, RichardZoller, KatrinBernkop-Schnurch, Andreas2023-11-282023-11-282023Kali, G., O?zkahraman, B., Laffleur, F., Knoll, P., Wibel, R., Zo?ller, K., & Bernkop-Schnu?rch, A. (2023). Thiolated Cellulose: A Dual-Acting Mucoadhesive and Permeation-Enhancing Polymer. Biomacromolecules, 24(11), 4880-4889.1525-77971526-4602https://doi.org/10.1021/acs.biomac.3c00577https://hdl.handle.net/11491/8714This 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 1H NMR spectroscopy. The thiol content was determined by Ellman’s test. The conjugate exhibited 215.5 ± 25 ?mol/g of thiol groups and 84 ± 16 ?mol/g of disulfide bonds. Because of thiolation, mucoadhesion on porcine intestinal mucosa was 9.6-fold enhanced. The apparent permeability (Papp) 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.eninfo:eu-repo/semantics/openAccessCellsCelluloseDyes and pigmentsInterface engineeringThiolsArticle24114880488910.1021/acs.biomac.3c00577Q1WOS:00108211800000137796043Q1