It was the aim of this study to develop mucoadhesive microparticulate delivery systems based on thiomers and to investigate parameters influencing their mucoadhesive properties. Microparticles were prepared via coazervation of thiolated or unmodified polycarbophil with fluorescein-diacetate as marker. The protective effect of the polymers toward enzymatic hydrolysis by intestinal enzymes was investigated. Mucoadhesion studies with microparticles, applied in dry and prehydrated form, were performed by ascertaining their residence time on intestinal mucosa. Furthermore, the influence of the amount of thiol groups on mucoadhesion was studied in vitro. Results showed that in comparison to unmodified polycarbophil, thiolated polycarbophil provided a more than 3-fold higher protective effect for the incorporated marker fluorescein-diacetate toward hydrolysis. When being applied in dry form 23.4 +/- 4.8% of the fluorescence marker being embedded in thiomer microparticles remained adhering to the intestinal mucosa within 3 h. In contrast, only 11.6 +/- 2.0% of the marker remained on the mucosa, when the thiomer microparticles were applied in prehydrated form. In addition, tests performed to assess the impact of the amount of thiol groups pointed out that a high amount of thiol groups is advantageous in order to further improve mucoadhesive properties. This knowledge should contribute to the design of highly efficient drug delivery systems being based on thiomer microparticles.