My name is Mark presents I'm
on the faculty in chemical and

by medical engineering at Georgia Tech.

I'd like to tell you about research
that we're doing in my laboratory on

the subject of drug delivery.

Our goals broadly are to use the tools

made available by engineering to solve
problems in medicine in particular

to deliver drugs more
effectively into the body.

We're trying to do things like take
back scenes protein based drugs and

other things that need to be injected
using a hypodermic needle and

administer them across the skin with
a patch without having to use a needle.

We're trying to do things like take
medicines for the i particular ones for

the back of the eye that are needed to
save site and to administer them also

without a hypodermic needle in a way
that is both simple and effective for

patients and a final topic
that we work on is the use of

again engineering technologies to
drive molecules inside of cells and

in particular gene based molecules
to realize genetic therapies.

So in my slide I have a summary of
some of the things that we are doing

the laboratory for drug delivery is
working on as I mentioned transdermal drug

in vaccine delivery ocular drug delivery
and intracellular drug and Gene delivery.

In the area of transdermal delivery.

We have a particular interest in
a technology that we call micro needles

in this case we take the power of the
microelectronics industry to make a very

small objects we don't make small
transistors instead we make Micron scale

needles that are assembled on a patch like
system that can be applied to the skin.

In the needles could be made in a hollow
form for infusion into the body and

we are doing studies using hollow micro
needles to deliver insulin to human

diabetics and are finding a faster
response that is the blood glucose level

is better controlled by
delivering insulin into the skin

where the uptake into the capillaries
is faster than if you deliver it.

Subcutaneously we're also working
with solid micro needles in this

case we coat the my current
Eagles with the med.

And of interest of particular interest
is influenza vaccine and other vaccines.

So we coat the vaccine onto this needle
patch we apply the patch to the skin

the coating dissolved
off in about a minute.

And then the vaccine
has been administered.

So there is there is no
hypodermic needle involved.

We expect there is no need for the
expertise of a doctor or nurse to do this

we envision the possibility of someday
where these patches could be available in

the pharmacy or mail to your home and
you could self administer the flu vaccine.

We also work on other vaccines
as well especially for

needs in the developing world where
clinical infrastructure is limited and

a simple vaccination
method would be appealing.

In addition to micro needles we
are interested in micro dermabrasion

Now some people know about this as
a cosmetic technique it's essentially

sand blasting the skin which can
make the skin look nicer for

those who choose to use it for
that purpose.

We're interested in a different purpose
we're interested in sandblasting

the very surface of the skin.

It turns out that the main barrier
to drugs entering into the body

lives in that very surface so
we can selectively scrape off

the micro dermabrasion that layer
without damaging the living cells below.

We could increase
the Skins permeability and

allow drugs to enter research
goes on in that area to

thermal ablation is another approach
that is related in this case once again

we want to remove the very surface layer
of the skin called stratum cornea and

instead of doing it by an abrasion
method we also do by a thermal method.

Namely we give a very short
thermal pulse short in time and

in very small space on the skin and
as a result.

Only the surface of the skin
heats up heats up enough to

to burn a small hole in the skin
mind your microscopical.

But not the pulse is sufficiently
short that there's no time for

the heat to propagate
deeper down into the body.

So once again we have a targeted effect
we can selectively remove the very upper

layer of Stratham cornea without causing
damage to the living cells that are.

Below and

research continues in that area also final
topic is that of poor forming peptides so

there are peptides that exist in nature
may gain ins are the are the prime example

that are on the skin of frogs they exist
in nature as a natural antibiotic that is

they insert into the plasma membranes
of bacteria they self assemble to form

pores which kill the cell by a mechanism
that isn't completely understood.

Our goal is to use these
poor forming peptides and

not to insert them into the bacteria
membranes but rather to insert them into

the membranes of the Skins outer layer
of stratum Corney and making Poor's and

that layer and
enabling drugs to go through and.

We have been able to
demonstrate that that occurs.

So those are some different approaches all
have a common theme of this thin barrier

layer on the surface of the skin prevents
drugs and vaccines from getting in and

if we can use various devices and
apply energy in the right way we can in

a very selective manner get across that
barrier in a way that we think patients

can self administer in a way that gets
rid of the need for a hypodermic needle.

Our second topic is ocular drug delivery
in this case drug delivery into the I

both to the front of the eye which is
typically done with eyedrops as well as to

the back of the eye which is typically
done with an intra ocular injection.

So once again the hypodermic
needle presents itself and

it's something that we
would like to get rid of.

So our ocular delivery research
involves again micro needles.

We are using both the solid needles that
are coated as well as the hollow needles

that can infuse but the common goal
here is to have a localization within

the I by using the micro needle and also
to use the needle not to prep penetrate

all the way across the eye but
just to go into the ocular sheath

that is the tissue that forms the the
shell of the eye but not to actually

pierce into the interior of the eyeball
itself which should be considerably safer.

So work that we're doing for
example is for

treatment treatment of
macular degeneration.

We're using.

Hollow micro needle to insert
just into this ocular sheath and

access an area called
the super coronal space.

That's about halfway and

it's not on the surface of the eye
it's not as as deep in as the retina.

It's right in between and

by targeting that space we can
infuse fluid into the eye and

the fluid then travel circum French
really around the eye and they this.

If you will the underside of the retina or

the choroid which is where our
drug targeting needs to be.

We're also doing work with the solid
needles in particular at the front of

the eye where we've shown for
example if you take I dropped and

put them on the ice surface.

Most of the drug just washes away
by the tear fluid that exists on

on the surface of your eye but
if we stake take the microwave and

stick it just into the cornea but
not across we can get

orders of magnitude more
efficient delivery into the eyes.

So our research in both of
these areas continues and

with both kinds of micro needles.

We're interested in slow
release implants as well.

The micro needle procedures probably
are something that would need

to be used in a doctor's office and
probably not for home self administration.

So in the scenario of longer term
therapy that is often needed.

We are interested in having a procedure
that might occur in the in the doctor's

office.

But then it can release drug for
a longer period of time and

there are polymer based systems
that exist to accomplish that.

In other contexts our interest in
particular is to leverage the tools of

the microelectronics industry
microphone advocation to make.

Micro fabricated devices that have
been etched and formed to have

this kind of a controlled release to
the eye over an extended period of time.

Finally extended release eye drops I
mentioned a moment ago that when you put

apply eye drops of the surface of the eye.

It's washed off very quickly by

the natural clearance mechanisms
of the I would which is good.

We want to keep our eyes clean.

However it's a problem because
it's not enough time for

a drug to penetrate into the eye and
have its.

Effect.

So we're working on formulations that will
keep the drug on the surface of the eye

for a longer period of time and the way
that we do it is a combination of three

things one of them is that we use
particles that encapsulate the drug and

we make those particles so that they
are coated with a new cohesive material

that is a material that likes to stick to
the mucus layer on the surface of the eye.

So we make particles that are sticky.

In addition we made particles then
same particles that are flat as well.

And so now when they're stuck
to the surface of the eye

instead of having a typically
spiritual particle

sticking up in the fluid flow
that wants to wash it away.

We now have the particle lying
flat on the surface where it gets

nice that he turned to the surface and
the fluid can wash over it more easily and

not carried away so that second feature
and the third feature is that we package

these various micro particles
loaded with a drug.

Inside of a more macroscopic particle that
might measure on the order of a millimeter

in size that is made of a rapidly
dissolving material and

this little particle then is placed
in what's called the cul de sac under

the lower eyelid place of that location
and the macro particle quickly dissolves.

But as it dissolves.

It's creating a high viscosity
environment in the eye

such that the little particles
that are embedded in there.

Don't just get washed away immediately but
instead they have some time to fall down

associate with the surface of the eye and
stick to it and then within a few minutes.

All of the macro particle material washes
away but we've given enough time for

the micro particles to stick and we found
that we can increase many fold the.

The time over which these particles
stay on the eye in this approach and

thereby increase the amount of
drug delivery into the eye.

So these are a few different things that
we're doing in the context of ocular drug

delivery the last topic that I'd like to
talk about is interest cellular drug and

Gene delivery or in this case the goal
is not to get across the skin or

get into the odd but on now a a much
smaller length scale getting within.

An individual cell and
crossing the cells plasma membrane.

We're interested in three
different approaches here.

One of them is through
the use of ultrasound.

Now ultrasound is widely known for
use in medicine in particular for

imaging we use ultrasound under
very different conditions so

the things that I'm about to
say do not apply when for

example a fetus is being image in
a pregnant woman very different conditions

are used in the conditions where something
called cavitation occurs cavitation

is the formation of bubbles which
will oscillate in the pressure field.

Ultrasound is a pressure wave.

So by applying ultrasound to a bubble the
bubble will oscillate with the high and

low pressure and in fact if you drive it
hard enough the bubble will collapse and

that energy release can have effects
on cells and that's what we study.

And what we have found is that if you use
ultrasound into the right conditions that

generates the right sort of cavitation
you can break open the cells membrane

make holes in the cell membrane
that are relatively large

that can be approaching a micron at
least hundreds of nanometers in size and

through that hall various things can enter
the cell such as the as the genes or

R.N.A. or other things that you
might want to deliver into the cell.

The cell that needs to repair itself and

it does it's an active repair mechanism
where the cell patches up the membrane

resealed it and survives the process
nicely if we have done things correctly.

So our work is focusing not only on the
longer term application of trying to put

real therapeutics into cells for
desirable medical applications but

also as looking at the mechanisms by which
the cell responds to having a whole put in

its membrane and
repairs itself in the process.

ELECTOR peroration accomplishes
some similar goals.

It's an electrically based method for
opening up the cell membrane but

mechanistically it's quite different.

It's related to a dielectric
breakdown it's like like curries and

I want to capacitor fails or a spark plug.

So we are in essence making a kind
of spark across the cells membrane

and in that way.

Creating small pores that.

Molecules can go through.

There isn't exactly a spark but
but it's a similar concept.

So there are these pores that
are made in the cell membrane and

again molecules can enter but in electro
peroration the pores are much smaller

they're on the order of one or
a few nanometers in size and they reseal

spontaneously they don't require any
active mechanisms of the cell to do it.

And finally the most recent work that
we're doing in this area is using

laser activated nano particles our
observation from the ultrasound

cavitation work is that we're interested
to generate turns out to be a shock wave

from these collapsing cavitation bubbles
and we thought maybe there are some other

ways to generate a similar kind of
shock wave that we could control better

the ultrasound cavitation mechanism we can
control pretty well but as you can imagine

we're applying ultrasound which makes
a bubble the bubble makes a shock wave and

so there's a number of steps that we all
have to control maybe we can get a little

closer to the generation
of the shock wave itself.

So what we do is we have some carbon
nano particles that are exposed to laser

in the near I.R. and that laser energy is
not absorbed by the water around it or

the cells but is absorbed well by
the carbon particles themselves.

So by giving a pulse of laser We've
tried nano second in femtosecond so

extremely short pulses of laser light
heats up these nano particles and

heats up to the point where they become
reactive with the water that surrounds it.

So the carbon and the water react to
form carbon monoxide and hydrogen.

So a solid in a gas a solid in a liquid
carbon in water form a gas and

a gas hydrogen carbon monoxide.

So there's a huge volume expansion
going to these very low density

gases that are produced and that
produces a shockwave which we can tune

very nicely you put in more particles
you put in more laser energy.

You can you can make these these
these a sudden gas expansions occur

in a controlled manner and what we
have found is the effects are quite

similar to what we see with ultrasound
we can open up the cells but

there are a number of advantages and one.

Of them that I think that is key
is that we're using nano particles

which can readily penetrate into
the spaces between cells in a tissue.

So we can infiltrate a tissue
with nano particles and

then hit it with laser in
contrast with the cavitation

the ultrasound cavitation bubbles
are typically of microns dimensions and

there isn't that much room
within a solid tissue.

So we think they're going to be some
advantages to using the Nano approach

rather than the ultrasound which turns out
to be more of a micron scale phenomena.

So I hope that gives you some sense
of the things that we're doing in

my lab at Georgia Tech.

We have these goals to
achieve drug delivery.

We're interested in three barriers
in particular the skin the I and

the cell membrane.

And we're trying to leverage a variety of
different engineering based approaches

to overcome those barriers and deliver
drugs genes and vaccines more effectively.