Covalently binding mucoadhesive polymers: N-hydroxysuccinimide grafted polyacrylates.

AIM: The aim of the study was to establish a novel type of covalently mucus-binding polymers by targeting selectively amino groups within mucus glycoproteins.

METHODS: N-Hydroxysuccinimide (NHS) was attached to carboxylic groups of polyacrylic acid (PAA). The reaction was mediated by the coupling reagent N,N'-dicyclohexylcarbodiimide (DCC) achieving polymeric NHS esters being able to form amide bonds with free amino groups. The chemical structure of the obtained conjugates was characterized via FTIR- and UV spectroscopy. Reactivity towards mucosal amino groups was evaluated UV spectrometrically upon addition of L-glycine. Furthermore, tensile force evaluations on intestinal mucosa as well as rheological experiments with mucus were performed in order to prove mucoadhesive potential.

RESULTS: Depending on the amount of NHS added to the synthesis, coupling rates of 876 to 1820 µmol NHS per gram polymer were obtained. Kinetic studies of amide bond formation showed a substrate dependent reaction velocity. Rheological synergism of PAA-NHS was proven by a 7.9-fold increased mucus viscosity compared to the control polymer. In further mucoadhesion studies PAA-NHS showed a 5.5-fold improved adhesion time compared to unmodified PAA. Tensile force evaluation confirmed these results with a 1.7-fold higher maximum detachment force (MDF) and 2.7-fold increased total work adhesion (TWA) for PAA-NHS compared to the unmodified control polymer.

CONCLUSION: The results of the present study provide strong evidence that coupling NHS to polymers could be a promising tool for the development of novel mucoadhesive excipients.