Scientists at the Hyderabad-based CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB) have developed a novel way to treat fungal keratitis. Keratitis is the inflammation of the eye, which starts with redness and itching and might eventually lead to blindness.
Keratitis can be caused by both bacteria and fungi. Fungi attach themselves to the cornea and release enzymes that break down the corneal proteins for their nutritional requirements.
In the process the cornea also gets inflamed. Corneal damage causes wound and scar formation leading to severe visual impairment. It is estimated that about 30% of keratitis cases in India lead to blindness.
Treating keratitis infection is currently a challenge because it is difficult to maintain a therapeutic dose at the corneal surface for long periods as blinking and tear formation washes off the drug. To address this challenge, a two-member team led by Ch. Mohan Rao of CCMB has developed protein-based nanoparticles that encapsulate the drug.
Certain antibodies get attached to the outer surface of the nanoparticles, thus anchoring the nanoparticles to the corneal surface.
The infected cornea expresses a set of receptors (TLR4) when infection sets in. The team has used antibodies to these receptors to anchor the nanoparticles to the cornea.
“If the infection is severe, more receptors are expressed on the cornea and more nanoparticles get bound to the receptors. Since they are bound, the residence time in the eye is long; neither blinking nor tear formation washes off the nanoparticles,” says Dr. Rao, the corresponding author of a study published in the journal Nanoscale .
Titrated cure
The enzymes secreted by fungi breaks down the gelatine protein of nanoparticles that encapsulates the drug, thus releasing the drug. Like in the case of the receptors, more enzyme is secreted when infection is severe leading to more drug being released from the nanoparticles.
“The gelatine protein acts as an alternative nutrient for the fungi. The fungi also degrade the gelatine-based nanoparticle to derive nutrients thus minimising the damage to the corneal tissue. In the process it releases the drug. In a sense, the fungi are committing suicide by consuming the gelatine protein,” says Saad M. Ahsan from CCMB and the first author of the paper.
The trials carried out on rats were encouraging on all counts.
As the residence time of the nanoparticle containing the drug is longer, the frequency of drug administration gets reduced significantly.
“In animal trials we found that application of the drug once every 12 hours was sufficient to completely clear the infection in seven or eight days,” Dr. Rao says.
As the use of antibodies on the surface of the nanoparticles makes the drug expensive, the researchers are working on designing a short peptide that can be used in place of the antibodies. They are planning to carry out one more animal trial on monkeys or rabbits before starting trials on humans.
