Polymers with thiol groups: A new generation of mucoadhesive polymers?

Purpose. To improve the mucoadhesive properties of polycarbophil by the int roduction of sulfhydryl groups. Methods. Mediated by a carbodiimide, cysteine was covalently bound to polyc arbophil (PCP) forming amide bonds between the primary amino group of the a mino acid and the carboxylic acid moieties of the polymer. The amount of co valently attached cysteine and the formation of disulfide bonds within the modified polymer were determined by quantifying the share of thiol groups o n the polymer conjugates with Ellman's reagent. The adhesive properties of polycarbophil-cysteine conjugates were evaluated in vitro on excised porcin e intestinal mucosa by determining the total work of adhesion (TWA). Results. Depending on the weight-ratio of polycarbophil to cysteine at the coupling reaction, e.g., 16:1 and 2:1, 0.6 +/- 0.7 mu mole and 5.3 +/- 2.4 mu mole cysteine, respectively, were covalently bound per g polymer. The mo dified polymer displayed improved internal cohesive properties due to the f ormation of interchain disulfide bonds within the polymer in aqueous soluti ons at pH-values above 5. Adhesion studies revealed strongly improved adhes ive properties. Whereas the TWA was determined to be 104 +/- 21 mu J for th e unmodified polymer, it was 191 +/- 47 mu J for the polymer-cysteine conju gate 16:1 and 280 +/- 67 mu J for the polymer-cysteine conjugate 2:1. Conclusions. Polymers with thiol groups might represent a new,generation of mucoadhesive polymers displaying comparatively stronger adhesive propertie s.