Function and Delivery of Antifibrotic Polysaccharides

Fibrotic conditions account for nearly half of all deaths in industrialised countries. Scarring in the eye can lead to blindness, and impaired healing following burns can lead to significant disfigurement and impairment. Additionally some conditions, such as epidermolysis bullosa, lead to progressive scarring of the skin and mucosa, triggered by the motions of everyday life. There is thus an urgent need for antifibrotic therapies that are not only efficacious, but also affordable, and more easily brought to market. To this end natural polysaccharides, which are abundant, low cost, and have a long history of use in food and pharmaceuticals, were studied for their antifibrotic activity. <i>In vitro</i> assays of epithelial fibrosis were utilised to assess the proclivity of the different polysaccharides to inhibit scarring, and understand which traits of the polymers led to increased antifibrotic action. Optical techniques were developed to probe the physicochemical mechanism of fibrosis inhibition, grafting fluorophores onto the polysaccharides, primarily to understand their interaction with transforming growth factor beta 1. The most potent antifibrotic polysaccharide, iota carrageenan, was then formulated for improved material properties. As primarily structural polymers, the therapeutic polysaccharides themselves can be used to provide the desired mechanical properties. Ionotropic, physical cross-linking under shear was used to create discontinuous fluids consisting of high-polymer density particles within an interstitial phase. These materials were viscoelastic, yielding improved retention at the target site, but also sprayable, owing to the breaking points between the discrete particles, for ease of application. Together, these findings suggest that single-component polysaccharide formulations may represent efficacious and affordable means to inhibit fibrotic conditions, with a simplified route to market.