April 10, 2015
2 min read

Nanotechnology under study to provide long-term treatment of glaucoma

Products in development may be a therapeutic option for patients with glaucoma who undergo cataract surgery.

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Drug delivery using nanotechnology is evolving, with expanding implications for glaucoma therapy, Jay S. Pepose, MD, PhD, said in a presentation at Hawaiian Eye 2015.

“It’s not surprising that glaucoma and cataract go hand in hand,” Pepose said, adding that even with expanding surgical options to treat glaucoma, including phacoemulsification alone, topical therapy is still the mainstay of treatment. However, topical therapy has drawbacks, including compliance issues, local and systemic side effects, peak and trough drug levels leading to 24-hour IOP fluctuations, and ultimately increased cost of patient care.

Jay S. Pepose


Current long-term drug delivery systems aimed at overcoming some of the drawbacks of topical therapy are limited as well, he said, because they are non-bioerodible, surgical insertion is invasive and complex, and duration of effect is suboptimal. In addition, there are size, chemistry and manufacturing limitations.

What is needed is a better delivery system, he said.


Nanotechnology is the manipulation of matter at the atomic and molecular scale to create materials with new and enhanced properties, Pepose said.

Nanotechnology products are already on the market, including ophthalmic drugs and devices, with some in development that have paradigm-changing potential, according to Pepose. But nanotechnology, too, has drawbacks.

“The eye really has a lot of options,” he said, with regard to potential ocular delivery targets such as contact lenses, punctal plugs or fornix-based devices. “But one of the limitations with current nanotechnology is the precise control of the formulation and the particle size.”

Particle replication in non-wetting templates

In “breakthrough” research, particles can be precisely engineered as small as 100 nm and as large as 1,000 µm using particle replication in non-wetting templates (PRINT, Envisia Therapeutics) nanotechnology, Pepose said. PRINT controls the size, shape, surface functionality, chemical composition, elasticity and porosity of the particles.

A silicone master is coated with a proprietary material, and then the drug is mixed in and cured with ultraviolet light. The formulations produce a suspension of harvested particles. Up to 50 g of particles can be created per day, with the potential to lower treatment costs, he said.

“What this does is it brings the precision and control of semi-conductors, like you would be etching a microchip, to the life sciences,” he said.

PRINT technology is also compatible with a number of pharmaceutical materials, Pepose said, including cyclosporine, dexamethasone, travoprost and anti-VEGFs.

Intracameral implant

“One goal [of glaucoma therapy] to date is to develop an effective extended-release prostaglandin formulation,” Pepose said.

An intracameral implant of travoprost, an extended-release formulation in a biodegradable polymer drug delivery system, can be tuned to deliver drugs over days, weeks or months, he said. The in vivo proof of concept has already been achieved in an animal model, with 30% reduction from baseline IOP in 8 months and no safety issues revealed with the single dose.

A clinical trial has begun in patients with both cataract and glaucoma, wherein the patient undergoes a washout period before implantation; then, at 4 weeks, cataract surgery is performed and the device is retrieved. Pharmacokinetic levels of travoprost are measured in the aqueous humor and compared with baseline levels. Residual levels of drug remaining in the implant are also measured.

Primary outcomes of the clinical trial are safety and efficacy, and secondary outcomes are a determination of the pharmacokinetics, systemic exposure and residual travoprost in the implant.

The first implants were inserted in January, Pepose said. – by Kristie L. Kahl

For more information:
Jay S. Pepose, MD, PhD, can be reached at Pepose Vision Institute, 1815 Baxter Road, Suite 205, Chesterfield, MO 63017; email: jpepose@peposevision.com.
Disclosure: Pepose reports financial interest in Alcon, Allergan, Bausch + Lomb, Doctor’s Allergy Formula, Envisia Therapeutics and TearLab.