For the good stuff from our profit
center these officers at the school of

chemical engineering
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Me on my previous research for so many
years is also director of the central for

my design development there were two of.

The boxes on this B.S. degree from
Stanford and disappeared from MIT for

the chemical engineering is
the census focused on my physical.

Drive through a big show in my life
the last mile if that's the sound

basis of experience and I think this is
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these teams sent into it and
at the border for

a price that's almost over the.

Papers here and if you're honest I'll
say yes or five studies I should up

finding friends party
like us conferences and

you know so right on the time that's
true and so forth are fun to talk or

these you know there are prostitutes
behind but I don't mean to be ice

to the eye using my head.

Thanks very much for the introduction and
please keep keeping it specially

if what I'm saying is interesting enough
you'll get a little extra energy from

the food hopefully you won't
take a nap after the food.

With my grenadiers is probably more known

in the context of micro needle patches
that are used for administer drugs and

vaccines to the skin but there's also
been a very significant effort for

many years to develop micro needles that
are suitable for delivery in the eye

now when we think about the my cradle
patches for the skin a lot of our

emphasis is it's something that's
painless and something that patients.

Can do at home very easily by themselves
that's not the value proposition in

the eye we're not anticipating sticking
micro needles in people people sticking

like reals in their own eyes that a
proposition is a different one and namely

it's a bad proposition of targeting that
we can use very small needles to place

drags precisely within the eye at the
place they need to be for their side of

action and so they're not at other places
where they could cause side effects.

So here is a picture of the eye and
I guess if you've been here this morning

you're already well aware of the I
have been thinking about it but so

that the front of the right of
the cornea is shown on top and

of course the lens the retina and
yellow around the back and

there are two scenarios for drug delivery
to the eye even though you're talking to

someone in the front part of the eye and
then you will probably take eyedrops and

some of the drug will get absorbed
in one of the diseases in the back

of the line it's probably in the retina or
the crude that pink is the choroid and

then increasingly we'll get an interview
trail injections and an injection here and

the drug goes around or you might have
other kinds of injections around the liar

you might even take the drug systemically
So those are the root of the two camps and

drug delivery they are the front and
the back and so

it's a little bit about drug
delivery in each of those contexts.

A brief introduction to
red micro needles on and

there are four flavors of them which I'm
I'm showing here apologize in the context

of skin but the ideas are the same
in the case of the eye and so

run scenario is that you have micro
needles that you puncture into the skin or

into the eye you pull it out and
now you have some holes and

things can go through those holes at a
much greater rate than they would have not

gone through say the cornea you
put holes in the epithelium And so

the drug can be absorbed more
readily through those holes and

the other scenarios you put
the drag on to the micro needle.

Self So

when the microscope penetrates into the
tissue the drug coating dissolves off and

then you pull those needles out and you've
deposited your drug in an active manner

within the tissue bill you shot that is
to make the needles rather sizable So

it's the same idea the needles in and the
NIH her micro needle desires as opposed

to just having a coating dissolve off and
then the fasten it was a hollow my cornea

don't so that's more like the hypodermic
needle and syringe that we normally think

that it's now a liquid formulation that
you actively inject the flow through

I've shown here might be my corneas could
be one could be multiple micro needles.

Depending on what you're doing you might
want to use a different kind of design

as you'll see right I talk about
today it will be two of these so

there will be the coated micro needles and
there will be the hollow micro needles.

So here is the summary of that line of
what's to come so the first topic will use

the coated micro needles and will treat
issues in the front of the ice so

it'll be interesting moment delivery using
sad micro needles into a straw meaning in

the stronger of of the cornea and
will begin delivering Bevis's you

mad an anti the Jaff compound and
a body to treat corneal And

you know that's who has ation and
then the second one is super Caruthers or

livery using highly micro needles and Dr
grass the class alluded to that before but

will go into a little more detail on
what super cradle delivery lives and

there be three septuplets there
are different kinds of drug delivery

strategies how do you see formulations
how to achieve targeting and

then we have a game we play
with gravity as you'll see.

So let's start with the first
topic friend of the hour topic and

the interest Romel delivery and there are
cases where there can be something within

the cornea that needs treatment run
example would be if there's an injury to

your eye that injury part of the response
to that injury can stimulate bread vessel

growth into the cornea that's not so
good your cornea that.

Normally bread vessels for good reason
you'd like to see through a transparent

Korea so that kind of revenue
growth he would like to prevent and

says That's our objective here is to
have an interest stromal delivery

within the cornea to treat injury
induced knew that scholars ation and

were using the coated needles for
that So here is a little cartoon of that

because I did my career's have
been pressed into the corner.

And then the coating does absolve
you pull the needles out and so

now you have a targeted delivery of
the drug right within the cornea.

But it can also be a dread that gets
further absorbed out of the cornea into

the front of the eye in this particular
case that's not our objective and for

something a big molecule like bed this is
the map that absorption will be relatively

small but for a small molecule that can
diffuse more easily than there could also

be used for delivery to targets deep in
the eye for example to treat glaucoma.

Here's a picture of a coded Micronesia
also this is a single micro needle it is

so you describe it it's about
seven hundred microns in length

you can see coated some green dye on it
we stick it into tissue pull it out and

the coating dissolves off.

And that picture to it to give you some
further sense of scale and here's again

one of those neighbors it's now with some
coding you can see this the different

color this one isn't fluorescent and
next to it is a conventional drop from and

eye dropper given to the eyes so
again the the numbers are small and

a micro needle is apt and it's important
because the cornea is quite thin and

so we need to make our needles very
short this one is a five hundred microns

deal which is what we're using for
the intro corneal delivery.

So here is the experiment
that we have done

the way we've induced an injury in
the cornea is by putting a suture in and

indeed that happens in the case of
corneal transplant the new cornea gets so

sure Don And I commend do need a basket
as ation as a result of that but this is.

A modern more Bradley for any kind of
injury that could be in the eye and

here you can see the the edge of the
cornea is over here it's off the screen so

that's the edge of the corners where
the cornea meets the right of the eye and

there are of course blood vessels
in your in your school or

in the white of the eyes you can
probably see after a late night out.

But there aren't supposed
to be bred vessels here so

here you can see the suture and these
red vessels have started to invade in

to deal with that injury we then took
Bevis's Emad which again is this anti bed

Jaf compound that Geoff being vascular and
feel of growth factor so an anti bed Jeff

prevents you know that's killers ation
from occurring we've had a topical his

eye drops that big molecule does not get
absorbed really ran across the cornea up

the theory arm and as a result there
are lots of ASCO which are there as well.

In the case we ran.

The injury and we met that red vessel
growth starts and then we treated it so

that you know the doctor noticed that
you got your prescription you went to

get your treatment and so this is the
interest around using my county those and

you can see the bread vessels started to
grow in but then they were stopped and

they didn't keep going in so it was as
you'll see with a more qualification

with this approach seems to be a rest stop
for the progression of the disease but

it doesn't cause
a complete reversal of it.

Sam quantified the lead to to show
what I've just been describing So here

is the new vascular is ation everywhere so
we did some image ourselves on the I so

I read what fraction the I was was
read had read vessels in it and

you can see then if we
have an untreated eye that

the new That's realisation increases and
then it sort of reaches a peak plateaus or

maybe decays a little that's just
the natural course in the rabbit model for

new That's who are stationed
with this injury.

We could then use a micro
neither placebo and

it's basically the same not surprisingly
we command given a topic or

delivery about this is a map and topic
of delivery means three times a day for

two weeks and in aggregate the total
amount to live it is fifty two and a half

thousand micrograms fifty two milligrams
and you can see we had some effect.

The final case is using the my critique
a single treatment with my cornea was just

a better less one time giving Fairpoint
for micrograms and that single treatment

which cruder deep area of drag right
where you needed it to be where the.

Sutures place you can see then we did
an even better job that having to give

eyedrops three times a day for four
week or for two weeks and the breeders

expressed again here we just set the date
ten in the day eighteen values and

you can then compare them and each of the
different cases and again makes the case

that this is a single targeted delivery
with a microbial work the best among these

different scenarios we do try and
the other scenario as well so

here again is the I'm treated case
where asterisked act said conjunctiva

injection so this is an injection under
the conjunctiva is a is a clue right

there that sits right on top of the square
at which is that right layer so

we make an injection between members
to read at the edge of the cornea and

it's a liquid injection and some of
the drug can diffuse in from there.

So in the case and said conjunctiva
the injection with a little bit was

that is the same dose we give with Mike or

he also nothing happened because some
of the drag actually reached its target

we can then use the microwave or you see
that response or we can give two and

a half thousand micrograms of the drag
by said conjunctiva injection and

then when you when you do that
much drag in the less targeted

manner some of the bed is actually
going to needs to go and you can see.

The response is the same.

So we think their advantage to having this
very targeted deliver because the doses

small Are there can be side effects
associated with that this is a map and

in general with drugs if you
think this is a model for

other drug delivery scenarios as well.

You might be concerned that sticking a
needle in the iris is not a good thing to

do the rest certainly there you
would feel it and so there would be

topical anesthetic applied before somebody
might do that to you but in terms of

the level of injury that it causes so this
is five minutes after the insertion and

that's where the microbial have been
inserted into the cornea and you can see.

Basically you don't see anything so

it's extremely rare tolerated we basically
after a few hours you can't even tell

where that needle had
entered into the cornea.

So that's a snapshot into one scenario
where we'd like to target delivery in

to the cornea I'd like to spend the rest
of the time talking about the super

curricular route of drug delivery in
a few things that we've done there.

So as I mentioned a moment ago interview
true injection is the standard way in

which a drug would be delivered
to the back of the eye and

in this case you stick a needle into the
center of the eye you make an injection

of the new route in the drug
then the fuses out and

the drug goes where you want to go
that is it goes to the right and

then the choroid those are the sites of
most disease in the back of the eye so

that's where you really want to go have
a drug that's here in the middle is

it's not really relevant to therapy
it's just sitting there and

waiting to diffuse out but the drug
also comes out of the cornea and so

to the lens the drug can also get up into
the funny I it's not terribly right target

it's really flattering in the eye with the
drug for example in the case of steroids

this can be a real problem steroids
are often injected into the eye to treat

inflammation and indeed it goes to really
needs to go but the contacts the lens.

And extended exposure of steroids through
the lens often causes cataract surgery

gets into the front of the eye extended
stary treatment in the eye often causes

comma so it is a removal variation to keep
the drug away from this part of the eye

and really keep it focused right here
where you need the treatment to occur so

I push that is through the use of
a single heart or a micro needle and

here is conceptually
what we would like to do.

And this will happen or
stand the anatomy for those who aren't so

familiar the right here is
the square on the right of your eye

the pink is the color red
which is the vascular tissue.

Off right here is the retina which
is the nervous tissue that sees and

then the true is humor is filling
the center which is basically hydrogen so

as to have a microwave of the close
a crass the scriptura no deeper just to

the interface of the square and the cord
and make an injection at that interface

turns out of the script and the court are
not tightly attached to each other they're

just sort of resting actually each other
and the rhetoric separated so what happens

is when we make an injection at that
interface the path of least resistance is

for the fruit to forever with the gap
between the square and the choroid and

closer come French really around
the eye within that space Well I've

mentioned before the target that we'd like
to hit is the corridor in the screen and

this provides us a way to
hit exactly that target and

not Fred the whole eye with the drug.

You saw Dr grass across the in my image so

here it is again similar home I could do
was that we made this mike and you know.

There's a half in there with me to wrong
it's smaller than just the batteries on

a thirty inch needle thirty gauges already
a small needle that's what's used for

interventional injections easily and
I had to put it at school and

there you can see the needle
right at the tip.

I don't see if I had any
better luck with movies so

this is a movie showing and
I from a rabbit here is the optic

nerve sticking out the back the cornea
is on the front you can't see it and

this is an older version of the micro
needle but anyway this is a bill and

you can see it at the very tip of that
Holder is this very tiny microbial and

what we're going to do is inject India
ink so black ink into the supercritical

space.

All right well I came
prepared on this one.

I don't make it go away right.

And I do have the movie here as

a backup.

OK let me inject I just started
saying to Fred I'll take my word for

it it's flowing within a super creative
space so hopefully prove that to you later

and within just a matter of seconds we
reached here the back of the eye and

ear the optic nerve its substantial
area of the eye has now been covered

after this injection.

There's about said I've got another
movie let's not just try my luck and

I'll discuss straight to the movie here.

So just to orient you first to rights
going on this is an ultrasound image of

the eye so there at the sound is looking
you know in front from the surface and

looking in toward the interior so

this is the surface of the on the probe
has been well placed right about it

this is the cornea which then
meets sap with the square and

the squares continuing around the back the
corner in the red not immediately below

the square conjunctiva on top of that this
is the iris the people is right here.

This is where the fun part of the I
as defined by the I was in the lens

meets the back part of the eye and we're
going to make a super critical injection

that is a needle that's going to come
in around here someplace and it's going

to then flip through then and right should
happen is there should be a separation

between the square on one side and
the cord and retina on the other side and

that action is all going to
take place right in there so.

How to Have a look and see if you can
follow it ultrasound sometimes hard to

follow.

After all that build
up now hero maybe I'm.

Going real slow.

I don't know why it's playing so slowly.

And I think much is really happening.

OK Here you go it's starting.

To.

Play.

And I move it along

here.

Anticipation.

All right well brass is here in
the audience he took the movie celebrates

the movie didn't work it's not
your fault it's worked in the

past.

Here's a cross sectional
cross section of through and

I read of the super cradle injections
the end two segments of the cornea

is over here we go round this is the post
where the optic nerve is somewhere over

here you can see the side where the need
to rest Preston across the square and

then there's a very thin
line here the ejection

contained within that super chordal space
going so come frankly around the eye.

And then a bit of information to hopefully
convince you of this localization this is

a a frozen section of the I this is normal
I have the cold I mentioned is a vascular

tissue so it's a little bit radical in
the vasculature the retina below and

then we can do a similar section after
injecting India ink black dye and

you can see the dollars
below the square and

just a bag of the pinkish choroid so.

We're pretty convinced that this is
a way to target the drug right into

that thin space of super chordal space.

So now what can we do with that well
there's a few different scenarios that

might be of interest in one case we
might want to keep the drag right

at the site of injection we might not
want it to float away and that's because

in the case of Gras coma
the similarly body is here and

the similar body produces
the humor in your eye

in Greco-Roman as in every bit of
pressure in your eye so red of the reason

which is treated is you turn down the red
of a commission with production and

that and it was the pressure in the eye to
be reduced so there are some drugs that do

that and we might like to put
the dragon immediately adjacent to the.

Body and have a very targeted anti-growth
common drug delivery there and

then accuses we might want to
deliver Bradley across the cord and

the retina and have full coverage of the
ice on some of the other images we didn't

go completely around the eye we
just had pretty good coverage but

let's can we get complete coverage so
it will be two scenarios in interest and

we worked on formulations to try
to get that kind of targeting.

So here's a picture after getting a super
critical injection without special

formulation where a brand is a fluke and
I bar and the cornea is down

the optic nerve is up would then slice it
like an orange and then put it out for.

Our pedal image so this this is where
the Rams and the corner are and

then all of these points would connect to
each other at the very back of the eye

let's interesting to look at is under the
four essence optics that's after making

injection of a read that you can see that
there's a lot of it that is in the super

close space but it doesn't cover the hair
I it's just a reasonable fraction of

the ladder that it got delivered to so
how might we change that.

Well run things that you
might think about is that

the size of a deliver could matter so we
delivered particles of different sizes and

you can see as you scan across that that
didn't seem to make much difference in

terms of what percent of the I got covered
were also left as a function of time and

you might think those particles might move
around in there well they don't really

move around in there with every coverage
you've got of the time of injection

that's pretty much what you've
got doesn't change too much so.

That could be good or bad we think
the reason that's happening is that

making injection into the space
in this particles will go in but

then the fluid that you've injected gets
absorbed it goes away in the space goes

back down again and
the particles are trapped.

Them rather to try to look at formulations
that could help us with this problem and

in order to do that we wanted to
have first we wanted to look or

as the particle so
here is the keep it by the super.

Batty type of approach and for that we run
polymers that were extremely We she were

running so sure thinning means that this
guy said he was living under sheer and

it's hard without sheer will run
a really very short because we need

to inject the stuff of this when I discuss
it he will never injected it and but

runs it's endless of record especially
want to get extreme of this case so

that nothing will flow and everything will
stay right with lace where the injection

was made and so here you can see in the
case of this ninety Care lot methyl said.

As well as the seven hundred killed on
car boxing at the sunrise there's a very

she you're thickening the discusses very
hard here at the very low sugar and but

it sort of has come down
to a little this custody.

So using that kind of an approach
we've looked at how that might affect

the coverage of the eye and you can see
that for the for the one of the good ones

here the seven hundred kilogram C.M. suit
over the course of two months we did get

a pretty good radicalisation by the time
after two months there was some spread but

that if you compare to
the the ninety caravan C.M.C.

which is not as sure thinning at the time
as the injection it was the same keep

it local as at the time of the injection
but shortly thereafter it may be wrong or

kept it localized so it got diluted out
in the C.M.C. probably diffused away and

we didn't retain things resurrect not as
Match of the ninety killer down nothing so

Rose we only looked out
to fourteen days and and

that was doing a good job over that time
so we think this kind of approach of

playing with the disconsolately is a real
to look for as the drug where you want it

to be now medicine would like to do is
to get the spread as I'd mentioned and

they are thought Well as we would like
something that is sure thinning but

not as sure thinning we still want to be
remembered Cassidy for the injection but

we don't want such a high discuss it
afterwards because we do want it to spread

and I grant here is to keep the supercross
space open so that particles can move.

Here's what we found so if you make
the injection just with saline.

Or in a day fourteen you've injected
it's cover a reasonably good area and

then nothing changes and

you can do different volumes we've all
been to this nine hundred fifty killer

drug high ironic acid at the time of
injection it's very medicalize because

we've made a suggestion it's pretty
discus I remember you can see that one.

To me it's later there's been a lot
of spread that's occurred and

we can think about what the mechanism
might believe suggested one mechanism but

many cases observation is that subsequent
to the injection there Reza spreading that

occurred we didn't actually get any better
than then certainly in say land use and

that another thing called Discover schizo
actual commercial product use in the eyes

can drop in sulfate and hieratic acid and
we concentrated out as much as four X.

concentration and you can see finally
we got to one hundred percent coverage

completely removed these these particles
throughout the supercritical space and

there's a picture at one of those flower
petal images so you can see everything is

red within the supercross Spence the part
that isn't red is the part where

the superclubs face ends and
it becomes the front of the eye.

Using the these observations we
then run it to try to see if

we could actually treat in a useful
way by targeting the delivery so

when Here's another weather picture of
a micro needle next to the next and

I dropped the comparison here girl coming
up take I drops multiple times a day.

And as I mentioned before I was to talk
of this levee right next to the so

we are the body.

This image I think shows nicely
cross-section through the eye here is the.

Here is the core of injected material into
the supercross space which is expanded

we captured it right at the beginning when
it was still expanded he was the iris here

is the center of the body and
the cornea is over here lens over here so

you can see that back injecting into
the most anterior part of the Super Crew

the space which we call the Super Series
space you're right next to the ciliary

body and he was another image where
we've done the same thing here is this.

Her body here is a very much expanded
super so early space with some

particles in it over time this would
close down as as the fluid is absorbed.

We're using that approach.

And anti-graft come a drag Ramana Dean
it's many patients use we want to do you

know as part of their therapy and
we measure the interocular pressure

in the rabbit eye so this is the change
in interacting with pressure and

the barriers to lever the interocular
pressure we have a few different scenarios

say our first one is a topical
eye drops a bit Monody in.

And if you look at the screen you can
see what that that looked like so

there was a drop given a little bit of
delay of the interocular pressure drop and

then there was a recovery we then
injected into the super crater space for

monitoring at three different doses and
at the middle steps it wasn't quite

as good a response but
of the two higher doses the responses

were quite similar to what we
saw topically But note that the.

Point seven five is one hundred times
less of a dose than topically and

that's because we have this very
targeted delivery and it shows that by

delivering sort of from the back door
coming in behind the superhero space

the drug can serve the fuse up into the
sillier body just like it can from topical

eye drops but
just much less efficiently with topical.

Asset supercritical injection as
well tolerated here is the rabbit

eye at different times this is
where the injection site is and

you just you can't see very much it's
a small needle it's very well tolerated.

So it's.

Really interested in doing injections
monitoring every day we're interested in

getting an injection response and
having the effect last a long time.

It was six months of therapy because
many graft coma patients will see their

doctor every six months so

you go see the doctor get a shot there and
drops for the next six.

Once we start with the baby step of one
month we work with a collaborator who

formulated party rock to
CO Greg KARK acid particles for

slow release of Bronstein and
who's the change in interactive

pressure before it was an Alice
now it's in Billy's and

you can see conjure out of the rise of the
untreated eye and so that's our control is

not much going on a little noise better
in the day and the hour that received

this super critical injection of slim
responded in a single injection a day zero

there were significant reduction in the
interocular pressure that extends out for

many weeks so we think this is
a nice proof of principle or

at least that we can put a control release
formulation right next to the ciliary body

and control interocular
pressure over an extended time.

We had a man to experiment with we enjoy
it we did a super cool injection of

particles that had no drug in it and
interestingly there is some effect

from Matt not as much and not as long
lasting but the reason effect of that and

I'm interpretation is that these particles
are keeping the super critter space open

and that is providing a pathway for
the equally as human to fret out

from the front of the eye that's getting
into a little more esoteric topic for

those who are more familiar with glaucoma
but interesting observation to include.

The rason that like to tell you a bat
is a route to target the drug and or

to the back of the eye maybe you want to
tell you to the macular to treat macular

degeneration for example and
I think it was let's use gravity

to do that let's put some particles
in the eyes that are heavy and

positioned there are the right way and
let the particle sink down and

I just put equations there
I'm not going to talk them.

Which probably makes you all happy so
you do have to be roommates and

particles that has a preferred Bekele and
so that is a prefer a color that is used.

In the body and
it has a density of two six.

Then we put some solid particles around
and these are simulating some particles

that contain drug in this case
they just were fluorescent and

the idea was that you make an injection
in the super cradle space the space

expands with ADD the fluid that you put
in and the particle store that space and

then your particles can start to sink and
they have to sink quickly that

sink to the back of the lobby for
the super credit space closes up again but

if they do then the I
can close up again and

trap the particles in the back of
the eye where we want them to go.

Here's a get it over to send out
a movie this is this is a picture we're

all familiar what you've seen
before on the phone injection and

then we can look afterward so here is
five seconds after the injection you can

see the supercross cradle
space has expanded

thirty seconds of staring to close at a
minute ten minutes so we have a sense for

how much time we have before the Super
crowd of space closes and then really it's

pretty quick I do really within a minute
we'd like to have the particles sink.

Here some of these particles that are just
the scraps of the performer carbon

is in the center of that the red particles
sitting at that interface interface

this is something called
a Pickering a mansion for

those who are interested in
interface will science but

it's rare that you can have these kind of
particles at the interface of a babble

in a liquid we made them
have three different sizes.

What we found was that for
use the big runs

Rican we find that within right after this
is within thirty seconds the particles

sink down about this is a centimeter and
that's about the diameter of the rabbit

I say a proof of principle sir looks like
these particles can sink the distance and

of the eye diameter within well under a
minute so we ran with them as serial would

happen actually when the eye and
here's what we saw So this is these

thirty five micron particles with the
cornea down so this is the opposite this.

The particles are going to go
to the front of the eye and

you can see when we qualified we divide
the the eye into these quadrants so

this is the very front of the super credit
space this is the back is approaching

the macula optic nerve you can see that
the particles very heavily have a roof

over the front of the eye and
if we did exact same experiment just for

the rabbit or for and have the cornea
now up you can see very different

distribution now we didn't get everything
in the very back quadrant of the IRA but

we certainly got a lot more of it
to grow into the back of the eye

as compared to this.

We also run a test lab and
once we get them in the back and

I do they send you there because if they
were to start moving I want to wrap it

runs around of the start moving all
over the place not hatful and they do.

The profile here is that
they found the profile

not much has changed
the particles seem to be trapped.

So that brings me to the end of this or
for

that given you Sam some ideas
about these my computers and

how they could be useful in the eye for
a targeted delivery whether it's to

the front of the eye into the into
the corner for example or the back of

the Ryan how we can formulate things there
we get into that super critical space but

move things around and look arise
them writhe in the Supergirl space so

that we have very tight targeting of
the drug just where it needs to go.

I'll acknowledge many people who
have been involved with research and

I rather not have them did the work I
show this is every everybody and without.

And the talk or any

questions.

Ok Ok so many times said the same
thing can you say what I should hear

as just a cutting desire going off and
we read.

On the ice for
thirty seconds to let that dissolution

occur.

Now it's just it's literally a dissolution
process it's very very rather somber

materials that are coated on the needle so
they desire off when they're in

water.

We haven't had infection to be a problem
if you think for example red stone and

cataract removed and which is done
after time on a routine basis

a much bigger one was made in the cornea
to do that actually multiple holes if you

think of intra betrayal injections we make
our super cradle injections at the same

rotation on the eye is the interviews
are all injections are but they're much

more shallow and use a smaller needle and
say if we make some comparisons to things

that are already done and clinical
practice we rarely rarely except that we

think we're doing similar things
except even less invasive.

First of all it's not really my expertise
the question you asked bad my sense of

I don't think we're doing something
to address the issue that you really

we're delivering the drug that.

We hope a constant dose designed
to be at a constant dose and so

if that drag loses its effectiveness
then you would need to use a different

dose.

OK let's say again I did not
knowing much about this topic but

that sounds like thank you for that

suggestion.

But you can talk to Bradbury's The expert
who's developed the method bed with

them so for those who haven't seen how
it's made us start out with a ironic

can you laugh and then they bring
a grinding to a man and cut it down and

grind that that better onto it and that's
fine when you have a Romney needle but

if you want to get close to a better
shared needle you can't use a screening

tools because they're going to bang into
the the head that hurts that there's just

no room to get the least conventional
grinding tools in said Robert Miller

developed is a way to use a laser to do
that so we use a laser cutting method to

make them.

I resent guns will use them in our
experiments but but certainly for

any human use they would
absolutely be single use.

In general we wouldn't be interested to
have a micro needle residing in tissue for

a month that wouldn't be convenient so
not the micro come in and out quickly but

then it leave something behind and
if we family that we've left behind so

bad it's a slow release then we can
accomplish your goal and so for

example with the brim on a name for the
group home a treatment that's a case where

we had medical particles found the real
need for slow release the need it was just

then for seconds but then the particles
were made it had that slow release so

that the kind of approach
that I think is most useful.

We have we have some preliminary
experience with with putting saddles or

putting viruses or putting D.N.A.
into the supercritical space but

it's I mean you can do it is all I can say
now about it we don't have any real data

to know is it functional Is there some
benefit to it we haven't done enough to

know that.

Yes.

So I think that in many cases an even
distribution would be desirable

I guess the question is how important
is it clinically to really have

a completely even distribution and
I think probably nobody knows because

no one has been able to do this before and
be able to answer that question but

let's go through the expectation
that it really would be better to.

That even distribution so
we are trying to use some other methods to

move the particles around within the super
crowded space and it's through to let you

know if anything works or not maybe next
year or what will have those results but

we are still trying to work on that
to make it more even or and or more

targeted.

At Georgia Tech as far as we grow is.

Rabbits However I think there's some
mention made before that clear side by

medical It's a company that was
started out at Georgia Tech.

In the clinic they have finished phase one
two clinical trial and now have two Phase

two clinical trials ongoing those
are are with delivery triumphs and

alone a set a knife so that is a steroid
drug that drag is formulated for

slow release two months or
same rate of release of the drug.

And so it's being injected into the
supercross space where it sets it slowly

releases the steroids and

is designed to control inflammation
in the eye keeping that so

I had a little from the front of the eye
where it can cause cataract and got home

but I think.

Dealing with that
question one runway is to

recognize that there may be some
variability in the thickness and

then account for what are the other to
somehow make some kind of measurement and

measure that they can assist and
then use the appropriate needle.

So really push can certainly be
done you can use an ultrasound and

measure the thickness of the square and
then pick pick the needle for that that's

a little bit cumbersome to do so
we have had to remove it from doing that.

But we do and
the rabbit Torii with experienced hands

you can feel where it is so if you try
to make an injection in the square

it's very hard there's a lot of back
pressure so you can just feel as as

a little bit of them as soon as you
reach the bottom of the square and

then you get a nice prayer into the super
cradle space now in terms of what should

be done in the clinic we don't
necessarily want to have to rely on

that lever of expertise many
physicians will have it better but

we want to make the system as intelligent
as possible the clinical experience is

however that it is wrong as many things
action it was at the same space so

you identify where the limbus is
the interface of the cornea and square and

then you move back a few millimeters and
you make the injection then doctors

are used to doing that because that's how
they do interview through injections so

that minimizes the variation and we found
that in most cases a single leader length

is able to to work and
it may be that the solution is

to have two needles in a kit
where if in those few cases

where it doesn't work there's a longer
needle available that then would

work.

For.