LAUSR

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&mgr;mol 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.