MEDICAL DEVICE INNOVATION - Medical Device Daily

MEDICAL DEVICE INNOVATION 2010
A tiny silicone cup improves
drug delivery for eye diseases
By LYNN YOFFEE
Medical Device Daily Staff Writer
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 oneone-hundredth
of the dose we’d get giving it systemically,”
A. Linn Murphree, MD, director of the Retinoblastoma
Program in The Vision Center at Childrens 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
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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.”
(This story originally appeared in the Aug. 5, 2009, edition
of Medical Device Daily)
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