Researchers have successfully used hollow microneedles to deliver minute particle suspensions into the suprachoroidal space in rabbit, pig, and human eyes in vitro.
Fort Lauderdale, FL-A team of researchers has shown that microneedles can be used to deliver nano- and microparticle suspensions into the suprachoroidal space of rabbit and pig eyes. In the future, microneedles could be a primary component of a minimally invasive approach to drug delivery that also could reduce dosing frequency and offer clinicians better therapeutic control, said Samirkumar Patel at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO).
Patel is a doctoral candidate in the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology, Atlanta. He and his colleagues in the lab of Mark R. Prausnitz, PhD, a professor in the school, are carrying out research on biophysical methods of drug delivery using ultrasound, microneedles, and other approaches.
The researchers are collaborating with Henry F. Edelhauser, PhD, professor of ophthalmology and director of ophthalmic research at another Atlanta institution, Emory University, on the microneedle project.
More efficient, less invasive
The researchers are interested in microneedles for sustained delivery of drugs to the posterior segment because the needles are more efficient and less invasive than current ocular drug delivery methods such as topical application, systemic administration, or intravitreal delivery, according to Patel.
Previously, the Georgia Tech group reported research involved drug-coated solid microneedles. In a presentation at the 2007 ARVO meeting, Dr. Prausnitz's group demonstrated that microneedles could penetrate into sclera in vitro and cornea in vivo and deliver useful quantities of model drugs into ocular tissues.
For their current research, Patel and colleagues used hollow glass microneedles whose lengths ranged from 500 to 1,000 µm to infuse nano- and microparticle suspensions into the suprachoroidal space of whole rabbit and pig eyes in vitro by inserting across the sclera. By injecting the needles deeper than in the earlier experiments, they were able to deliver a larger volume of drug and a wider variety of particles into the suprachoroidal space, where they can be designed to provide controlled delivery, Patel said. Their experiments showed that they could deliver particles ranging in diameter from 20 nm to 1 µm and volumes of 15 to 30 µl. They also determined the pressures required for delivery, which depended on particle size, and the insertion depth for suprachoroidal delivery.
The team has been successful in duplicating the results in human eyes but has performed most of its experiments in animal models due to a lack of whole human eyes and the cost of obtaining them.
"Our next step is to try to do this in vivo so that we can figure out if it's effective, and if so, how long these particles will remain," Patel said. "One of the concerns is that, if we wanted to provide long-term delivery with this method, then we need to know the residence time of the particles in the eye. This is something that we can't do properly in vitro, so we will have to do in vivo experiments to figure that out."
He and his colleagues are also studying the distribution of the particles, determining where they go immediately after delivery and over time and what influence the size of the particle might have on distribution patterns. This information will be useful in fine-tuning this delivery method.
"If we could know the distribution and clearance beforehand, it would help us design more efficient particles for therapy," Patel explained.
Considerable work has been done in various locations to develop microneedles for transdermal drug delivery, but ocular delivery is a newer research topic, Patel said. Georgia Tech is sharing a National Eye Institute grant with several other schools, each of which is specializing in a different aspect of ocular drug delivery research. The objective is to develop a method of drug delivery to the posterior portion of the eye for the treatment of conditions such as age-related macular degeneration and diabetic retinopathy.
The Georgia Tech lab is focusing on microneedles, whereas Emory University partners are considered the experts on transscleral delivery. A group at the University of Pennsylvania specializes in characterizing the delivery, and researchers at the University of Colorado, formerly at the University of Nebraska, have expertise in designing particles.
"With this combined knowledge, we can put each piece together to design a very effective delivery method," Patel said.