Not sure the Ph1 tox is relevant to RB other than
Post# of 72447
A Tiny Silicone Cup Improves Drug Delivery for Eye Diseases
Physicians and researchers have, for years, tried to get drugs into the eyes without a great deal of success. Much of it washes away and also gets absorbed into the body's system. A tiny silicone cup sealed to the outer surface of the eye may provide a more effective method for the delivery of medicines for retinal and vitreous diseases such as cancer, macular degeneration and diabetic retinopathy.
"We can get higher levels of drug in the eye with one-one-hundredth of the dose we'd get giving it systemically," A. Linn Murphree, MD , director of the Retinoblastoma Program in The Vision Center at Children's Hospital Los Angeles told Medical Device Daily . "So the patient would get much higher levels with lower exposures and virtually none getting into the systemic circulation."
Murphree's work centers on treating retinoblastoma, a cancer of the retina that typically afflicts children, which calls for chemotherapy. Current treatment involves intravenous delivery.
"We wanted any type of system to get chemotherapy into the eye in a better way," Murphree said. So he and two other colleagues invented silicone cup, which differs from any sort of implant or insert currently available because it's non-invasive and is attached temporarily with a bioadhesive glue.
"Think about a coffee cup with a flattened rim," Murphree said. "When you turn it upside down, it has a wide flange in contact with the eye and a bioadhesive is used on the lip."
The device can be reloaded with medication as needed.
Known as the episcleral drug reservoir, it holds the potential to fundamentally change the delivery of medications for all eye diseases, according to a report delivered by Murphree last week at the Association for Research in Vision and Ophthalmology (ARVO) Summer Eye Research Conference on Ophthalmic Drug Delivery Systems in Bethesda, Maryland, where he explained that it works like an organ-specific transdermal skin patch.
The cup isolates the medication targeted to the eye from being absorbed into the blood stream. It delivers medications to the interior of the eye over long periods of time up to months.
Drops, periocular injections and intraocular injections are currently used to deliver medications to the eye but generally for short periods of time.
This work is being backed by 3T Ophthalmics (Irvine, California), which holds the associated intellectual property license.
The episcleral drug reservoir is inserted under the thin, filmy conjunctiva, or covering of the eyeball, to the sclera the fibrous, protective outer layer of the eye. The cup administers the drug slowly by passive diffusion through the sclera, where it reaches the retina and vitreous. The device is so small the patient's vision is unlikely to be affected.
With preliminary testing complete, Murphree is currently developing a protocol for phase I/II clinical trials in humans, focused on retinoblastoma, to take place in 2010.
Murphree's first focus, retinoblastoma, requires relatively large doses to achieve a therapeutic concentration in the retina. A byproduct is that the chemo destroys the bone marrow and depresses the child's immune system, often leading to secondary infections. All of this delays an effective administration of the drug and the ability to treat the cancer.
"Our preliminary research shows that once the cup is fitted, the child should be able go home for several weeks. Because the drug is being administered directly into the eye and not systemically, chemotherapy dosage levels will be much lower and the debilitating side effects will be reduced," Murphree said.
He has tested the device in rabbits and observed they didn't seem to feel discomfort when the cup was attached, nor did they experience side effects as they would from systemically administered drugs.
The device is 8 mm to 10 mm with a reservoir that is about one-tenth of a millimeter. Liquids, tablets or gels could be loaded in the cup.
"We've shown that we can get 30 to 40 times more drug this way than if you gave the same amount as an injection," he said. "The difference is that you maintain the concentration radiant across the eye wall. Theoretically it could deliver drugs as large as Avastin and as small as antibiotics or steroids. It can stay on as long or as short a period as you want."
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