Each year, the annual Association for Research in Vision and Ophthalmology (ARVO) meeting provides a look at the cutting-edge research and technology that is shaping the future of eye care. One topic that continues to intrigue me: nanotechnology. Practical nanotechnology is the increasing ability to manipulate matter on an incredibly small scale, presenting possibilities never before imagined.^1-3 Nanotechnology can be used in a wide range of manufacturing and technology areas, providing medical breakthroughs and possibilities never before imagined.

“Nanomedicine” and “biomedical nanotechnology” are the terms most often used to describe the hybrid field of nanotechnology. This science has lead to fascinating developments—new diagnostic devices, analytical tools, contrast agents (used in imaging parts of the body to highlight certain features) and drug delivery vehicles.² For example, in cancer treatment, drugs can be designed and delivered to specific cells. This significantly lowers the drug consumption rates and subsequent side effects by depositing the active agent specifically in the morbid region, only in the dose necessary for treatment.^1,2

Treatment options also include management with iron nanoparticles or gold shells, in the fashion of a “Trojan Horse.”^2,3 Implantable device applications abound; these are often preferable to the use of injectable drugs to avoid the pitfalls of first-order kinetics. In first-order kinetics, the rapid rise of drug may cause difficulties with toxicity and efficacy when the drug drops below the targeted concentration range.²

Nanotechnology has significant applications today in vision research. It is represented well in the literature both in determining causes and treatment of various eye related diseases, such as glaucoma, macular degeneration, and cataracts.¹

The 2010 ARVO abstracts are teeming with novel applications using nanotechnology, so I’ve decided to highlight a few of them this month. The following are categorized into drug delivery systems and gene therapy topic areas.

Sustained Drug Delivery
Several abstracts presented at ARVO this year look into the potential use of nanotechnology for drug delivery, either onto the surface of the eye or directly into the eye.

Investigators from Vista Scientific and the University of Massachusetts have used a process called nanosphere synthesis to improve drug delivery to the eye through the use of a contact lens (abstract #3419/D1036). Ciprofloxaxcin was encapsulated into biodegradable nanospheres and incorporated into a poly-HEMA hydrogel matrix. Synthesis was customized to achieve release of ciprofloxacin over an extended period of time. The pulse dose of the initial phase, followed by a slow release, was accomplished over two weeks.

This technology could provide much-needed sustained drug release, and it could also improve compliance by replacing the initial frequent treatment and the tapering dose therapy required for ocular surface infections. It might even be well suited for pre-, peri- and post-operative prophylactic treatment with antibiotics over an extended period of time following ocular surgery.

Scientists at Johns Hopkins Wilmer Eye Institute evaluated the use of intravitreal nanoparticles as a new system for sustained treatment of degenerative and proliferative diseases of the retina (abstract #432/D1136). They found no difference in coated or uncoated particles and no significant decline in the particles retained in the vitreous even after 30 days.

This technology may someday replace repeated injections of angiogenesis inhibitors in cases of retinal disease. Hopefully, these drug carriers can be retained for prolonged time frames in order to reduce the potential side effects of repeated intraocular injections often required to treat many retinal diseases today.

Another team at Johns Hopkins investigated the feasibility of intracameral injection of nanoparticles for sustained drug delivery to the anterior chamber for post-operative therapies (abstract #435/D1139).

Intracameral administration of antimicrobials and anti-inflammatory agents during intraocular surgery decreases the need for post-operative medications, but free drugs are cleared quickly from the anterior chamber (abstract #442/D1146). However, the clearance rate was reduced for the nanoparticle group vs. the control, suggesting that this approach may provide sustained delivery of postoperative medication for up to one month. Researchers also considered using intrastromal micro- and nanoparticles as loading medication doses for keratitis and corneal graft rejection episodes, with sustained intrastromal drug delivery.

Bio-engineers at the University of Western Ontario and the Ivy Eye Institute examined the feasibility of encapsulating and releasing protein drugs through nanostructured contact lenses (abstract #439/D1143). They used hybrid nanocomposites, including transparent inorganic nanoparticles incorporated into hydrogel lenses and biopolymer nanoparticles loaded in a hydrogel matrix. They showed that hydrophilic proteins (growth factors) are able to be loaded in different types of nanoparticles. The new hybrid nanocomposites used as protein carriers served ably as an alternative means for protein delivery, and the hydrogel film further prolonged the release profile for the water-soluble proteins.

Gene Therapy
A number of this year’s abstracts deal with the use of nanotechnology as novel vectors for gene therapy. Researchers from the Mason Eye Institute at the University of Missouri, along with scientists from Singapore and MIT,  investigated the gene transfer efficacy of adeno-associated virus and gold nanoparticles stabilized in polyethyleneimine vectors for delivering therapeutic genes into human corneal endothelium (abstract #433/D1137). Significant gene delivery into human corneal endothelium culture was detected with the vectors used in this study, leading researchers to conclude that these vectors are extremely efficient for delivering genes into endothelial cells. Further study is underway to define dose and toxicity levels of selected vectors for corneal gene therapy.

The same group of investigators found that disease conditions affect gold nanoparticle-mediated gene delivery in the cornea (abstract #434/D1138). Normal and laser-treated hazy rabbit corneas showed only a 5% to 11% difference in transgene expression, whereas neovascularized corneas showed up to 31% (p<0.05) more transgene expression compared to the other tissues. Optimization of gene delivery in various corneal disorders is apparently necessary for successful treatment with gene therapy.

A team of researchers from the Moran Eye Institute, the University of Utah School of Medicine, and the University of Colorado sought to determine the efficacy of plasmid-loaded nanoparticles (anti-VEGF-A) in the regression of corneal neovascularization in mice (abstract #440/D1144). The results: significant regression in corneal neovascularization vs. naked plasmid and controls. Anti-VEGF co-glycolic acid-loaded nanoparticles are an effective, non-viral, non-toxic and sustainable form of gene therapy for the regression of corneal neovascularization in the murine model.

Future Applications
Nanotechnology holds unlimited potential for drug delivery and gene therapy in all fields of medicine. We here at RCCL applaud the many researchers that have once again made the ARVO meeting memorable thanks to their plethora of novel investigations.

I encourage readers to explore the incredible number of abstracts presented each year. Reviewing the abstracts will give you a good sense of what’s in store for the future. Ophthalmic research is alive and well!

To read the 2010 ARVO abstracts and learn about more of this year’s cutting-edge research, go to www.arvo.org.

1. The A to Z of Nanotechnology. Treating Eye Diseases Using Nanotechnology. Available at: www.azonano.com/news.asp?newsID=6855 (Accessed April 2010).
2. Wikipedia. List of Nanotechnology Applications. Available at: http://en.wikipedia.org/wiki/List_of_nanotechnology_applications (Accessed April 2010).
3. Nanowerk. Nanotechnology treatment for most common cause of blindness becomes feasible. Available at: www.nanowerk.com/spotlight/spotid=3894.php (Accessed April 2010).