The eyes may be the windows to the soul, but for certain pathogenic fungi, they are home sweet home. These microorganisms can colonize the cornea, forming biofilm sheets over the surface of the patient's eye in a condition known as fungal keratitis. Over time, these infections can have devastating consequences: they can impair vision and even cause blindness.
Unfortunately, once they take hold, fungal biofilms are notoriously difficult to treat. The problem is that the active ingredient in antifungal eyedrops, amphotericin B (AMB), gets washed away every time the patient blinks.
Zibiao Li, Senior Research Scientist at A* STAR's Institute of Materials Research and Engineering (IMRE) led a team of researchers in exploring nanotechnology solutions for next-generation topical antifungals. The team hypothesized that polymeric micelles, an aggregate of surfactant molecules dispersed in a liquid, could act as tiny drug reservoirs to trap AMB on the eye's surface, thereby extending its therapeutic window.
Li and colleagues first synthesized the polymer solution using medical-grade copolymers as the base material for the eye treatment formulation. Next, they mixed in what proved to be the secret sauce—cage-shaped nanoparticles called polyhedral oligomeric silsesquioxane (POSS). These spheres enveloped hydrophobic AMB molecules, helping them to stick around the ocular surface for longer.
"The polymers can self-assemble into micelles, which can be used to encapsulate and load poorly water-soluble AMB as a topical treatment for fungal keratitis," explained Li.
To validate the efficacy of their new POSS formulation, the researchers used a mouse model of fungal keratitis. They found that POSS significantly extended the time that the treatment remained on the eyes of the mice compared to conventional AMB drops. This retention translated to a greater fungal-killing efficiency in the POSS-treated animals, all without any observable side effects.
"To the best of our knowledge, this is the first report of bio-adhesive micelles made of POSS-based copolymers as a safe and effective formulation for ocular fungal keratitis infection treatment," said Li.
Still, Li says the POSS formulation is not quite ready to hit pharmacy shelves just yet. The process of synthesizing the polymeric micelles first needs to be optimized before manufacturing at a commercial scale. "Furthermore, just like other types of polymeric biomaterials, sterilization could potentially be tricky when a large production scale is involved," added Li.
Moving forward, the researchers will further engineer the nanoparticles to create more targeted treatments for various fungal infections of the eye. They also plan to broaden the scope of their study to develop specialized delivery systems based on eye surface adhesion in hopes of achieving better corneal penetration and alleviating any inflammation. Together, these studies will help propel the bio-adhesive polymer field towards improved solutions for combating fungal keratitis.
The A*STAR researchers contributing to this work are from the Institute of Materials Research and Engineering (IMRE).
