Thiomers--from bench to market

Abstract

Thiolated polymers or designated thiomers are obtained by immobilization of sulhydryl bearing ligands on the polymeric backbone of well-established polymers such as poly(acrylates) or chitosans. This functionalization leads to significantly improved mucoadhesive properties compared to the corresponding unmodified polymers, as disulfide bonds between thiol groups of thiomers and cysteine-rich glycoproteins of the mucus gel layer are formed. Furthermore, enzyme- and efflux-pump inhibiting as well as improved permeation-enhancing properties are advantages of thiolization. By the covalent attachment of mercaptonicotinamide substructures via disulfide bonds to thiolated polymers these properties are even substantially further improved and stability towards oxidation even in aqueous media can be provided. Meanwhile, more than 50 research groups worldwide are working on thiolated polymers. For certain thiomers the scale up process for industrial production has already been done and GMP material is available. Furthermore, safety of thiolated poly(acrylic acid), thiolated chitosan and thiolated hyaluronic acid could be demonstrated via orientating studies in human volunteers and via various clinical trials. The first product (Lacrimera® eye drops, Croma-Pharma) containing a chitosan-N-acetylcysteine conjugate for treatment of dry eye syndrome will enter the European market this year. It is the only product providing a sustained protective effect on the ocular surface due to its comparatively much more prolonged residence time worldwide. Various further products utilizing, for instance, thiolated hyaluronic acid in ocular surgery are in the pipeline.

Keywords: In vivo studies; Mucoadhesion; Permeation enhancement; Thiomers.