Chitosan-graft-6-mercaptonicotinic Acid: Synthesis, Characterization, and Biocompatibility

Abstract

Thiolated chitosans are relatively new thiolated biopolymers exhibiting mucoadhesive, enzyme inhibitory, and permeation enhancing properties. A drawback, however, is their pH dependent reactivity. The aim of this study was therefore to develop a novel thiolated chitosan showing a non pH dependent reactivity of its thiol groups. For this purpose, 6-mercaptonicotinic acid (6-MNA) was covalently attached to chitosan by a carbodiimide mediated reaction. The obtained conjugate was characterized in vitro by quantification of immobilized thiol groups, cytotoxicity, in situ gelling properties, and disulfide bond formation at different pH. The synthesized conjugate displayed up to 973.80 micromol thiol groups per gram of polymer in reduced form. The polymer was nontoxic and showed in situ gelling properties. Furthermore, disulfide bond formation and therefore gelling properties occurred at various pH ranges. The reactivity of thiol groups was in the same range at pH 3 and pH 6.8. According to these results, chitosan-6 mercaptonicotinic acid seems to have some promising features to be used particularly for mucoadhesive formulations.

Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties

“…Thiomers are prepared by immobilizing agents with thiol groups, such as L-cysteine, thioglycolic acid, 6-mercaptonicotinic acid, or 2-imminothiolane HCl, on polymeric backbones like polycarbophil, chitosan, or sodium carboxymethylcellulose. [16][17][18][19][20][21] Their main advantage is the increase in mucoadhesion relative to unmodified polymers. Unmodified polymers interact with mucin layers via non-covalent bonds, such as ionic interactions or hydrogen bonds, whereas thiomers are thought to form disulfide bridges with cysteine-rich subdomains of mucus glycoproteins.…”

Synthesis, characterisation and in vitro evaluation of novel thiolated derivatives of polyallylamine and quaternised polyallylamine

“…This contributed to the relatively low levels of thiolation observed in Paa/QPaa-NAC conjugates as can be seen from Table 1. The relatively low coupling efficiency of the EDAC-mediated thiolation process has previously been reported by other research groups [25,27] working on the thiolation of similar polycations using EDAC concentrations ranging between 25-200mM and has been attributed to a side reaction of EDAC with the nucleophilic thiolate anion that results in the formation of an adduct that is subsequently hydrolysed to one of the reaction by-products, urea [32]. In contrast, the reaction of Paa/QPaa with 2-iminothiolane was observed to proceed with greater efficiency considering the relatively high levels of sulphydryl groups substitution obtained for TBA conjugates (table 1) .…”

Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review

“…120 The permeability through the mucosal surface can be enhanced by acid, thioglycolic acid, glutathione, and 2-iminothiolane are the aliphatic thiol-bearing ligands with functional carboxyl groups which form amide bonds with the amino groups of chitosan by carbodiimide to synthesize the thiomers of chitosan. 118,[121][122][123][124][125] CMs prepared by these thiomers exhibit strong mucoadhesivity, biocompatibility, and enhanced permeability and absorption after oral and nasal administration.…”