Microscope images of
a mouse eye (left) show that the polymeric imidazolium compound PIM-45 protects
the cornea by reducing fungal invasion into the cornea (right; fungi are
stained black).
Stable,
inexpensive and easy-to-prepare active ingredients for topical treatments
effectively clear a fungal eye infection
Pathogenic microbes that become encased within a
protective and adhesive polymeric coating, forming a biofilm, are among the most
difficult forms of infections to treat. Fungal keratitis, for example, is a
common form of eye infection caused by fungi that can form a biofilm on the
patient’s cornea, which if left untreated may lead to blindness. A novel pair
of antifungal compounds that clear these biofilms more effectively than
existing treatments has now been developed by researchers led by Yugen Zhang
and Jackie Ying at the A*STAR Institute of Bioengineering and Nanotechnology,
Singapore1.
Zhang, Ying and co-workers developed their compounds
from a family of antimicrobial materials called amphiphilic polymers. These
materials incorporate both polar and non-polar subunits, a characteristic that
is crucial to their function: the polar group helps to anchor the polymer to
the microbe’s charged surface, which allows the non-polar tail to then
penetrate and rupture the microbe’s lipid membrane. The researchers’ compounds
incorporated a polar unit called an imidazolium group. Interestingly,
previously developed imidazolium-based amphiphilic structures simply featured a
long-chain non-polar tail. However, in a modification to the usual design,
Zhang and Ying's team developed short-chain amphiphilic materials consisting of
repeating polar and non-polar subunits.
The researchers showed that the amphiphilic components
of these materials — named IBN-1 and PIM-45 — make them particularly effective
for treating biofilms. In tests against biofilm-protected fungal cells grown on
the surface of a contact lens, the team showed that IBN-1 and PIM-45 were more
effective than fluconazole and amphotericin B, the drugs currently used to
treat these infections. “The amphiphilic structure and its high solubility in
water allow our short-chain polymers to better penetrate the biofilms,” Ying
explains. Using mice, the team then showed that their compounds could curtail
fungal growth in the eye itself (see image).
As well as proving more efficacious than current
treatments, the compounds also offer several practical advantages. Amphotericin
B and fluconazole are fragile structures, requiring careful protection from
heat and light. “Once a package of Amphotericin B is opened, it can be used for
one to two days only,” says Zhang. “In comparison, our compounds can be stored
in water or a buffer solution at room temperature for at least six months.” In
addition, IBN-1 and PIM-45 are easy and inexpensive to prepare, he adds.
The team is currently working with industry to
commercialize the polymer technology, according to Ying. “We will also explore
other applications of these materials,” she says.
The A*STAR-affiliated researchers contributing to this
research are from the Institute of
Bioengineering and Nanotechnology
References
- Liu, L., Wu, H., Riduan, S. N., Ying, J. Y. & Zhang, Y. Short
imidazolium chains effectively clear fungal biofilm in keratitis
treatment. Biomaterials 34, 1018–1023
(2013). | article
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