Preactivated thiomers

Thiolated polymers - designated thiomers - show strongly improved mucoadhesive, cohesive, permeation enhancing and efflux pump inhibitory properties in comparison to the corresponding non-thiolated polymers. For certain applications, however, an even further augmentation of these properties would be highly favorable. In addition, thiomers are comparatively unstable because of being rapidly oxidized in the presence of oxygen. It is therefore the aim of this project on the hand to enhance the reactivity of thiol groups leading to a demanded substantial improvement of properties as mentioned above and on the other hand to provide stability of thiomers towards oxidation. In order to achieve this goal thiol groups on thiomers are pre-activated by the formation of disulfide bonds with ligands exhibiting a 2-mercaptopyridine substructure. Resulting pre-activating thiomers are evaluated in terms of improvement of properties described above in vitro as well as in vivo.

Within the project Preactivated Thiomers a new generation of thiolated polymers (thiomers) was developed. Thiomers are compounds of long chain-length exhibiting numerous sulphur substructures. Sulphur substructures are able to form bridging structures in the human body. These so-called disulfide bonds represent one of the most important bridging structures in living organisms. Preactivated thiomers display strongly improved properties in comparison to so far used thiomers. In particular the adhesive properties of thiomers on mucosal membranes such as the nasal or buccal mucosa was substantial improved within this project. Preactivated thiomers are able to form more efficiently disulphide bonds with mucus covering mucosal membranes. In this way these polymers are to a comparatively higher extent anchored on the target mucosa. As thiomers can exhibit a sponge-like structure, drugs can be easily incorporated and released again at the target tissue. Because of the prolonged residence time of preactivated thiomers on the target mucosa, the therapeutic efficacy of incorporated drugs can be strongly improved. In addition drug uptake can be strongly improved by preactivated thiomers. Consequently drugs can reach their target more rapidly and in a higher concentration. A further advantage of this new generation of thiomers is their improved storage stability. Thiomers of first generation were stable just in solid form, whereas thiomers having been developed within this project are even stable in liquid form. This improved stability paves the way for the development of liquid formulations such as nasal and mouth sprays or eye-drops. Because of these properties these novel excipients will likely find a broad application in various medicines in order to improve their therapeutic efficacy.