New drug delivery method may change pars plana vitrectomy

November 15, 2007

A novel method of delivering drug to the retina using Aerosolized nanoparticles delivered during the air-fluid phase of pars plana vitrectomy may allow ophthalmologists to intervene with the disease process. Research using the technology on pig eyes showed that it seems to provide an effective concentration of drug to the posterior segment tissues. This mode of drug delivery could be effective for treating various eye diseases during surgery.

Key Points

"Aerosolized nanoparticle drug delivery offers a unique opportunity to intervene with the disease process, pharmacologically, during a common phase of vitreoretinal surgery, namely the air-fluid exchange. This [mode] has numerous potential clinical applications using various drugs or combinations of drugs for specific retinal diseases," he said.

He and his colleagues at the University of Minnesota, Minneapolis, developed sodium fluorescein in an aerosol form in a concentration of 12 ng/ml. Six groups of pig eyes, three eyes per group, were studied using standard three-port pars plana vitrectomy.

When using the flow-through mode of delivery, the fluorescein particles were delivered with the aerosol via an infusion tube into the vitreous chamber; the flow rate was 300 ml/minute over 3, 5, or 10 minutes. Any residual particles of fluorescein were removed by a flow of pure air (without drug) at the end of the flow-through period.

In contrast, during the single-fill delivery mode, the fluorescein particles filled the chamber and the sclerotomies plugged (with the drug in an aerosol, left in the eye for 30, 45, or 60 minutes for the particles to accumulate).

Following both delivery procedures, the animals were sacrificed, and the eyes were enucleated, dissected, and prepared for analysis. The fluorescein levels were quantified with high-performance liquid chromatography assay and the ocular tissue levels determined.

The aerosolization process by which the sodium fluorescein was converted into particles generated a median particle size of about 400 nanometers, according to Dr. Olsen.

Fluorescein concentrations

Dr. Olsen and colleagues reported that the flow-through delivery method appeared to be more effective in delivering a uniform, higher-concentrated drug coating of the sodium fluorescein particles to the retina. The investigators compared the results when the retina was exposed to the fluorescein particles for 3, 5, and 10 minutes and found higher levels by 10 minutes in the retina and uvea. They also observed that the fluorescein mass in the retina/choroid or uvea was higher compared with the lens and sclera.

In contrast, evaluation of the single-fill method indicated that the amount of particles actually delivered was less compared with the flow-through method. The amount of fluorescein particles on the uvea was about one-third of that achieved with the flow-through delivery method, Dr. Olsen said. The mass of particles on the uvea reached a peak in a very short period of time, whereas that on the lens and sclera continued to increase over time. The single-fill method was more efficient, i.e., delivered more of the drug to the tissue relative to the amount of drug utilized in the total gas.

Detailed results of this study will be published in an upcoming issue of Investigative Ophthalmology and Visual Science.