Thiomer Technology

The bioadhesive and mucoadhesive properties of most conventional polymers are often insufficient for effective attachment to biological surfaces and mucosal membranes. These traditional polymers rely solely on non-covalent interactions, such as ionic and hydrogen bonds, which limit their adhesive strength. In contrast, thiolated polymers, or thiomers, offer a significant advantage. They can form covalent bonds with cysteine-rich subdomains of membrane-bound proteins and mucus glycoproteins. This covalent bonding—mimicking the natural disulfide bridges commonly found in biological systems—results in markedly stronger and more durable adhesion.

To improve the bioavailability of non-invasively administered drugs, permeation-enhancing drug delivery systems are often essential. Thiolated polymers have demonstrated strong permeation-enhancing effects for drug absorption across mucosal membranes such as the intestinal intraoral and nasal mucosa. Unlike most low molecular weight permeation enhancers, thiomers are not absorbed through the mucosal surface. This enables a longer-lasting permeation effect while avoiding systemic toxicity from the auxiliary agent. The underlying mechanism of this effect has been elucidated, showing that thiomers act by reversibly opening tight junctions and leveraging glutathione as a permeation mediator. Since this mechanism differs from that of conventional permeation enhancers (e.g., fatty acids), a synergistic effect can be achieved by combining both systems. The permeation-enhancing properties of thiomers have been validated in numerous in vivo studies.

Maintaining a sustained therapeutic drug level is particularly beneficial for compounds with a short elimination half-life, as it reduces dosing frequency and improves patient compliance. While traditional polymeric delivery systems aim to control drug release via diffusion, their effectiveness is often limited by rapid disintegration or erosion of the carrier matrix. This limitation can be effectively overcome using thiolated polymers. During the swelling process, inter- and intrachain disulfide bonds form, significantly improving the structural stability of the polymer matrix. As a result, controlled and sustained drug release over numerous hours can be reliably achieved.

In situ gelling systems offer significant advantages across various life science applications. In drug delivery, they enhance the performance of topical liquid formulations—such as ocular, nasal, and vaginal products—by undergoing a sol-to-gel transition upon application. This transformation prevents rapid drainage and prolongs residence time on the mucosal surface. These formulations are administered as liquids and subsequently form stable gels directly at the target site.

In situ gelling properties are also crucial in the development of hydrogels used as bioinks in 3D bioprinting. Gelation can be triggered via oxidation or thiol-ene reactions. Oxidation-mediated disulfide crosslinking, for example, can be significantly accelerated by the presence of oxidizing agents (e.g., hydrogen peroxide, periodate) or enzymes (e.g., peroxidase). For instance, the addition of hydrogen peroxide to thiolated chitosan has been shown to produce a 10,000-fold increase in viscosity within a few minutes, highlighting the efficiency and responsiveness of this system.