aim of this thesis was to prolong mucosal residence time of drug delivery systems. Two strategies, namely, thiolated polymers or thiomers and zeta potential changing nanocarriers were developed. For the first strategy, novel thiomers were differently synthesized via amide, amine and amidine bond formation. Thiomers were alternatively generated by direct modification at hydroxyl groups of polymeric backbone. Moreover, preactivated and entirely-s protected thiomers were synthesized in order to protect reactivity of thiomers. The newly synthesized thiomers showed improved mucoadhesive, cohesive, efflux pump inhibitory and permeation enhancing properties compared to their corresponding unmodified polymers. These properties of preactivated thiomers were even more pronounced due to the fact that pyridyl ligand acts as a leaving group. With regard to the application of thiomers, they were demonstrated to be useful as the pharmaceutical excipients for oral, intra-nasal, buccal, ocular and intra-articular delivery. In case of the second strategy, zeta potential changing self-emulsifying drug delivery systems (SEDDS) and polymeric nanoparticles were developed. Various cationic surfactants and phosphatidates were incorporated into SEDDS and showed a shift of a zeta potential after enzymatic cleavage of phosphate by intestinal alkaline phosphatase. Negatively charged SEDDS showed higher mucus permeation, on the other hand, positively charged SEDDS were entrapped within mucus network. Furthermore, nanoparticles composed of phosphorylated polymers and cell-penetrating peptides-polymer conjugates exhibited improved transfection efficiency that could be highly potential approaches for gene delivery. Therefore, the use of both thiolated polymers and zeta potential changing nanocarriers provided promising tools to prolong residence time on mucosal membranes.