Thiolated Cellulose: A Dual-Acting Mucoadhesive and Permeation-Enhancing Polymer

Abstract

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 12.5fold higher than that of the aqueous solution of the drug. Results of this study show that the modification of cellulose with 2mercaptosuccinic acid provides mucoadhesive and permeation-enhancing properties, making this thiolated polymer an attractive excipient for oral drug delivery.

Bottom‐Up Synthesized Glucan Materials: Opportunities from Applied Biocatalysis

“…[ 358 ] In fact, thiolated celluloses have been reported for their interaction with biological tissues different from plain cellulose. [ 359 ] Using 1‐thio‐β‐ d ‐glucose as acceptor, “thiol–cellulose” (average DP ∼8) was synthesized and shown to assemble into nanosheets of cellulose II crystallinity. [ 334b ] The thiol surface groups enabled the templated assembly of silver nanoparticles (2.2 g silver/ g cellulose material) in a high yield of ≥95%.…”

“…[ 334b ] The thiol–cellulose can be an interesting material for numerous applications in the applied life sciences. [ 359b,360 ] Point recognized while studying the synthesis of thiol–cellulose [ 346 ] was that the CdP enzymes from different sources differ intrinsically (i.e., at the level of highly purified enzyme) in the degree that they can hydrolyze the αGlc1P donor substrate. The glucose released by the hydrolysis can compete with the β‐glucoside acceptor for cellulose chain polymerization.…”

Biopolymer Drug Delivery Systems for Oromucosal Application: Recent Trends in Pharmaceutical R&D

“…The mucoadhesive film demonstrated 88% in vitro drug release in 12 h and 80% ex vivo penetration of carvedilol through goat buccal mucosa in 12 h. However, non-ionic polymers are characterized by poorer mucoadhesiveness compared to polyelectrolytes [50,51]; therefore, their chemical modification with adhesive functional groups is used to improve mucoadhesiveness [132]. For example, Kali et al [133] prepared cellulose modified with 2-mercaptosuccinic acid by reacting cellulose with Sacetylmercaptosuccinic anhydride. The synthesized conjugate contained 215 µmol/g thiol groups and 84 µmol/g disulfide bonds.…”