Claudia Menzel
University of Innsbruck, Austria
Title: 2,2’Dithiodinicotinyl ligands: Key to more reactive thiomers
Biography
Biography: Claudia Menzel
Abstract
The goal of this study was to establish a new type of preactivated thiomers showing comparatively higher reactivity with mucus
and improved mucoadhesive properties. The dimeric form of 2-mercaptonicotinic acid (MNA-MNA) was directly attached
to the polymeric backbone of chitosan (CHI) to achieve a higher reactivity. Amide bond formation mediated by 1-ethyl-3-(3-
dimethylaminopropyl) carbodiimide (EDAC) was used as a coupling reagent. The remaining free amino groups were reacted with
succinic anhydride (Succ) to gain a homogeneously anionically charged polymer (CHI-Succ-MNA-MNA). Within our study, various
coupling rates of up to 170 μmol MNA-MNA per gram polymer were obtained. The coupling of the dimeric ligand resulted in
a preactivated thiomer with a more reactive disulfide substructure due to the additional nitrogen atom in conjugation over the
aromatic moieties. Furthermore, the obtained polymer is completely preactivated and therefore protected against unwanted oxidation
reactions. Our kinetic studies of disulfide exchange reactions showed a 3.8-fold higher reactivity of CHI-Succ-MNA-MNA compared
to a state-of-the-art preactivated thiomer. Rheological measurements showed that CHI-Succ-MNA-MNA with a coupling rate of 170
μmol (CHI-Succ-MNA-MNA 170) lead to a 5.7-fold higher mucus viscosity than the non-thiolated control polymer (CHI-Succ).
This indicates a rheological synergism due to mucoadhesive properties. These results were confirmed by an additional mucoadhesion
experiment, which showed a significantly prolonged retention time of CHI-Succ-MNA-MNA on the small intestinal mucosa
compared to CHI-Succ (P<0.02). According to the presented results, the double preactivation seems to be a promising strategy to
obtain entirely preactivated polymers with improved mucoadhesive properties.