Preactivated thiomers: their role in drug delivery.

INTRODUCTION: Since thiolated polymers - known as thiomers - have entered the pharmaceutical arena in the late 1990 s, more and more academic and industrial research groups have started to work with these promising polymeric excipients. Meanwhile, various thiomers are the subject of clinical trials and the first product based on thiolated chitosan will reach the market in 2015. Due to the formation of disulfide bonds with mercaptopyridine substructures, thiol groups of thiomers are on the one hand more reactive and on the other hand are protected toward oxidation. These so-called preactivated thiomers representing the second generation of thiomers are subject of this review. AREAS COVERED: Within this review, preactivated thiomers are classified and their mode of action is described. Furthermore, different synthetic pathways, purification and chemical characterization methods of preactivated thiomers are explained. Their properties including mucoadhesive, permeation-enhancing, efflux pump inhibitory and in situ gelling properties are described. In addition, various formulations based on preactivated thiomers are introduced. EXPERT OPINION: The first-generation thiomers have already shown great potential resulting in various product developments. Preactivated thiomers - representing the second generation of thiomers - offer the additional advantage of even comparatively more reactive sulfhydryl ligands and of stability toward oxidation. According to this, they are promising novel polymeric excipients for various applications.