Nanotechnology holds potential for ocular infection treatments

Molecular engineering suggests that nanotechnology could someday offer new treatments for various diseases.

The future holds promise that engineering of various nanoparticles could potentially revolutionize the treatment of ocular infections.

There are no immediate ophthalmic applications for nanotechnology, according to Y. Jerold Gordon, MD, but the theoretical concepts that are currently under development in various specialties could someday be applied to diagnostics, anti-infectives and drug delivery for ophthalmology.

“We are at the beginning of a hugely exponential growth curve of how nanotechnology will affect our lives,” said Dr. Gordon, who directs the Charles T. Campbell Ophthalmic Microbiology Laboratory at the University of Pittsburgh Medical Center.

Dr. Gordon shared an overview of nanotechnology at Hawaiian Eye 2007 and spoke with Ocular Surgery News about possible future ophthalmic applications of this growing technology. Dr. Gordon based his presentation on the work of his son Assaf T. Gordon, MD, of the Department of Rehabilitation Medicine at New York University, who has written extensively on nanotechnology and its future role in the field of rehabilitative medicine.

Nanotechnology is defined as research and technology development at the atomic, molecular or macromolecular scale, leading to the controlled creation and use of structures, devices and systems with a length scale of 1 nm to 100 nm. Research in this area began in the 1970s, and the technology is currently being used in materials for golf ball manufacturing, spill-proof pants and sunscreen.

Medical applications

Y. Jerold Gordon

“It is a field that begins with the engineer and the chemist. They are the ones who have created the molecules and the capability to work on the nanoscale. The question remains, how can you take the product of physical chemistry and structural engineering and apply them to the broad field of biology, the narrower field of medicine and the even narrower field of ophthalmology,” Dr. Gordon said.

“Medical applications only comprise 8% of this huge effort,” he said. “Since the year 2000, there has been a great increase in the number of publications, which include areas of tissue engineering, imaging, drug delivery, gene delivery, diagnostics, and surface coating and texturing.”

Drug delivery

Drug delivery may be one of the most effective potential uses of nanotechnology in ophthalmology.

The controlled slow release of therapeutic drugs, which is currently being targeted for use by retinal subspecialists for treating intraocular diseases, is something that may be achieved through nanostructures.

Nanostructures, which are chemically engineered, may also be used topically and subconjunctivally to treat the anterior segment, Dr. Gordon said.

“Drug delivery, as I see it, will be useful as nanocarriers to deliver specific drugs to targeted tissues. These nanostructures can also be engineered to increase penetration through the epithelial cells in the cornea and the conjunctiva,” Dr. Gordon said. “While this approach is theoretical, experimental ‘proof of concept’ has been achieved for antivirals, antifungals, anti-inflammatories, glaucoma medicines and anti-angiogenic medicines delivered topically to the eye.”

Anti-infective potential

The first real use of nanotechnology in clinical research is not as a drug carrier, but an engineered nanomolecule that itself possesses anti-infective properties, Dr. Gordon said.

Starpharma, a company in Australia, is developing a chemically engineered polymer, VivaGel, as an STS microbicide that works by inhibiting herpes simplex virus-2 (HSV-2) and HIV. The drug received fast-track status from the U.S. Food and Drug Administration for development.

“VivaGel represents the proof of concept. It is the first example of any nanotechnology structure that has demonstrated anti-infective activity in early clinical trials,” Dr. Gordon said.

If this nanomolecule is effective, it would be a “very short jump” to apply its technology to ocular HSV-1, which is a major cause of corneal infection.

“There are about 300,000 cases of herpetic keratitis a year, and it is a blinding disease,” Dr. Gordon said. “If VivaGel proves to be effective against HSV-2, it would likely work against HSV-1, which is a less pathogenic virus than HSV-2. To formulate this molecule as an eye drop or gel for ophthalmic use is a distinct theoretical possibility.”

Tissue engineering

Tissue engineering is another important area for advancement in ocular applications, Dr. Gordon said. Nanotechnology may be used for wound sealing in cataract surgery, penetrating keratoplasty and traumatic lacerations.

“We can use a photopolymerizable dendrimeric adhesive, much like a super glue,” he said. “It is also being developed like 5-FU compounds to prevent scar formation in glaucoma surgery.”

Another experimental use of tissue engineering is neural regeneration, Dr. Gordon said.

“The principle here is that we create nanostructures which are scaffolds,” he said. “They self- assemble, and they serve for regenerating nerves to find each other to regenerate functional nerves.”

During his presentation at Hawaiian Eye, Dr. Gordon presented the work of Ellis-Behnke. A video was shown of a hamster that had had a portion of its optic track destroyed surgically, producing visual field blindness. The animal was unable to follow a sunflower seed in its right visual field.

After 6 weeks of treatment with self-assembling peptide nanofiber scaffolds, the animal was able to recognize and follow the sunflower seed again.

“This is really the first demonstration in the central nervous system type lesion showing a full recovery with return of functional vision,” Dr. Gordon said. “This is really important for spinal cord injuries and optic nerve injuries, but with all technologies, such as nanotechnology, there are significant cautions.”

Despite the broad potential that the field may offer, there is still a need to address the issues of short- and long-term safety to humans exposed to nanostructures, he said.

“I agree with those who say we need measured critical scrutiny in the area of safety as we progress,” he said.

Diagnostic uses

Nanotechnology could also someday make Petri dish cultures a thing of the past, according to Dr. Gordon.

“For diagnostics, the holy grail has always been the laboratory on the chip,” he said. “We envision someday that a patient with an ocular infection will come to our office. We will take a specimen from the tear film or cornea and place it on a microchip. Five minutes after placing the chip into a small machine, we will get a digital readout identifying the microbial pathogen. The old traditional culturing will be history, and the Campbell Laboratory will need to devote its energies to other challenges in ocular microbiology.”

For more information:

• Y. Jerold Gordon, MD, can be reached at 203 Lothrop St., Room 935, Pittsburgh, PA 15213; 412-647-2212; fax: 412-647-5880; e-mail: gordonjs@upmc.edu. Dr. Gordon has no financial interest in any technology discussed in this article.

Reference:

• Ellis-Behnke RG, Liang YX, et al. Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision. Proc Natl Acad Sci USA. 2006;103(13):5054-5059.

• Daniele Cruz is an OSN Staff Writer who covers all aspects of ophthalmology, focusing on optics, refraction and contact lenses.