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Chapter Activities - 2011
October

On October 13, 2011, Samirkumar R. Patel, Ph.D. presented "Targeted Drug Delivery to the Eye Enabled by Microneedles." Diseases of the eye such as age related macular degeneration and glaucoma can be a challenge to treat because delivering drugs to the target site is not straightforward. Current drug delivery methods are dominated by strategies that poorly target the effected tissues and are often invasive. Microneedles offer an alternative delivery method that allows for targeting of the diseased ocular tissues in a simple, minimally invasive way that is not possible by current methods.

We demonstrate that solid coated microneedles can deliver drugs/model compounds to the anterior of the eye with a bioavailability of two orders of magnitude higher than conventional drops. This would enable treating diseases of the anterior of the eye with much greater efficacy. The surface of the microneedle can be coated with a drug formulation, inserted into the cornea, and the drug formulation dissolves off the microneedle, leaving the drug within the cornea.

Of greater challenge is delivering drugs to treat diseases of the choroid and retina located in the back of the eye. Delivering to the suprachoroidal space (SCS), between the sclera and choroid, may provide an alternative drug delivery route to treat diseases of the choroid and retina because of its close proximity to the site of action. The SCS is a virtual space in the eye that only within the last decade gained attention as a possible drug administration route. We present here a novel, minimally invasive delivery strategy employing hollow microneedles that can locally target the choroid and retina. This work demonstrates the ability of a hollow microneedle device to successfully administer an array of formulations into the SCS in a minimally invasive way. A single hollow microneedle can deliver small molecules such as steroids, large molecules such as proteins, and particles ranging from 20 nm to 10 um. We further show that this method is more effective at targeting the chorioretinal tissues compared to a conventional intravitreal injection and with an optimized formulation can deliver drugs to the posterior segment for months.

Samirkumar Patel attended the University of California at Berkeley and received a dual Bachelors of Science degree in Chemical and Material Science Engineering in 2004. He worked in Research and Development for Alza Corporation, a drug delivery company, designing controlled release oral formulations. He received his doctoral degree from the Georgia Institute of Technology in Chemical Engineering with a focus on ocular drug delivery in 2011. He is currently a postdoctoral fellow at Georgia Institute of Technology and a co-founder of a medical device start-up company specializing in targeted ocular drug delivery.

The IEEE EMB Society is grateful to Dr. Patel for giving this presentation.

April

On April 21, 2011, Dr. Paul Garcia presented "Waking Sleeping Beauty. GABA antagonists and their potential role in reversal of general anesthesia." Research in my laboratory focuses on the neurophysiological mechanisms that underlie inhibitory brain circuits. Enhancement of inhibitory pathways of the brain naturally lead to the familiar quiescent states of sleep and anesthesia. However, modulation of inhibitory networks in the brain also has profound implications on attention, memory, pain, and anxiety. Quiescent activity that resembles sleep or the anesthetized state is not unique to complex organisms like mammals and birds but has been observed in fruit flies, nematodes, and yeast; emphasizing how important these inhibitory circuits are to brain function. An organism's response to injury also influences the inhibitory signaling pathways in the brain. As both a practicing anesthesiologist and a scientist, I became interested in preserving neuronal function in the perioperative period, the common links between natural sleep and anesthesia, and the restoration of functional circuitry after manipulation of inhibitory networks through drugs that sedate or make one unconscious. Most of my work focuses on the pharmacologic manipulation of mammalian brain circuits which use the most abundant inhibitory neurotransmitter in the central nervous system, gamma-aminobutyric acid, GABA as their chief signaling molecule.

Dr. Garcia has his Ph.D. in Biomedical Engineering from Georgia Tech and his M.D. from Emory University School of Medicine. He is currently an Assistant Professor in Emory University's Department of Anesthesiology. As a clinician-scientist, he not only works in the hospital as a practicing anesthesiologist but also manages an active laboratory research program. His background is in Neuroscience/Bioengineering and his clinical interests are in anesthesia for neurosurgical procedures and neurologic disease.

The IEEE EMB Society is grateful to Dr. Garcia for giving this presentation.

January

On January 20, 2011, Dr. Laveeta Joseph presented "Conduction Block in Peripheral Nerves: Effect of High Frequency Stimulation on Different Fiber Types." The potential clinical and neurophysiological applications related to spasticity suppression, pain management, bladder control, and graded motor control for neural prostheses have warranted reliable techniques for transiently blocking conduction through nerves. High Frequency Alternating Current (HFAC) waveforms in the kHz range have been found to induce a reversible and repeatable conduction block in peripheral nerves; however the effect of these waveforms on the neural activity of individual fiber types is currently unknown. Understanding this effect is critical if clinical applications are to be pursued. Experimental work on the sea-slug, Aplysia, has shown that block induction through HFAC stimulation can occur in unmyelinated nerves. However, unlike simulations and experiments on myelinated nerves, a monotonic relationship between frequency and blocking thresholds was not observed in these unmyelinated fibers. To resolve this discrepancy, we investigated the effect of HFAC stimulation on the compound action potential of the sciatic nerve of frogs. The A-fiber and C-fiber components of the compound action potential were blocked at different stimulation amplitudes depending on the frequency of the HFAC waveform. Although the A-fibers demonstrated the monotonically increasing threshold behavior observed in published literature, the C-fibers displayed a non-monotonic relationship, analogous to that observed in the unmyelinated fibers of Aplysia. This unique behavior of the unmyelinated nerves could have several implications for applications related to selective stimulation of specific fiber types. Overall, this works demonstrates that HFAC waveforms can enable inherent peripheral nerve properties to be exploited for potential clinical applications related to the treatment of unwanted neural activity.

Laveeta Joseph recently graduated from the Dual-degree Technology Leadership Program at Georgia Institute of Technology, Atlanta, during which she concurrently pursued a PhD in the Interdisciplinary Bioengineering Graduate Program and an MBA from the College of Management. She received her BE degree in Biomedical Engineering in 2004 from Osmania University, Hyderabad, India, and ranked first among the graduating class. She then joined the Laboratory for Neuroengineering at Georgia Tech for doctoral studies in neural electrophysiology. Laveeta has received several awards for her doctoral work including the SfN Graduate Student Travel Award (2007), the IEEE Neural Engineering Conference Fellowship (2007), and the NIH sponsored NIC 2010 Excellence in Neural Interfacing Award. She was also granted the Schlumberger Faculty for the Future Fellowship from 2007-2010 for her scholastic potential. Laveeta recently completed an internship as a Systems Engineer in the product development group of Medtronic Neuromodulation and hopes to continue a career in the medical device industry.

The IEEE EMB Society is grateful to Dr. Joseph for giving this presentation.

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