Hello, and welcome to this episode of the
Physics World weekly podcast,
which focuses on a fascinating
aspect of space medicine.
Physics World's Tammy Freeman takes up the story.
Spending time in space has a big impact
on the human body and can cause a
range of health issues.
Many astronauts develop vision problems
as microgravity causes body fluids to redistribute towards
the head, which can lead to swelling in
the eye and compression of the optic nerve.
While eye conditions can generally be treated with
medication,
delivering drugs in space is not a straightforward
task.
Eye drops simply don't work without gravity.
To address this problem, researchers in Hungary are
developing a tiny dissolvable eye insert
that could deliver medication directly to the eye.
The grain of rice sized insert has now
been tested by an astronaut on the International
Space Station.
So I'm very pleased to be joined today
by two members of the development team,
Zoltan Nagy,
director of the department of ophthalmology
at Semmelweis University,
and Diana Bologweiser,
associate professor at Budapest University of Technology and
Economics
and lead researcher at SpinSplit.
Welcome both to the podcast.
So my first question
is why are vision problems so common among
astronauts?
I think it's a very interesting question. The
detailed and complete pattern mechanism of vision problems,
among
zero gravity is still to be
perfectly,
clarified.
However,
since we're, zero gravity, it causes fluid shift
in the human body. So it can cause
edema in the head and also in the
central nervous system
and especially within the eye.
It's called a neuro ophthalmic problem. So SUNS,
spaceflight associated
neuroocular syndrome.
And so it can cause a vision problem
for the astronauts and especially in long term,
space shift.
And,
we know that,
in the near future,
the human race is,
trying to make a long term,
spacecraft to the, let's say, to the Mars
or whatsoever.
And so they can cause an oedema in
the macular area. This is the most sensitive
part of the eye, and it's responsible
for sharp visual acuity.
So we,
if we know about this, then we should
do something.
And, there's a medication,
a nonsteroid
anti inflammatory drop, which if we administer,
then it can prevent
and treat,
the edema of the macular area.
But it it is a fluid.
So, therefore, we thought that we have to
do something because among zero gravity,
drops are really not working.
So so what what's the main problem? Why
why can't we use the drops in space?
You know, then in amongst zero gravity, the
absence of gravity, dosing of fluid drops is
nearly impossible
because it evaporates in,
in the air,
due
to instability of the drops. And placing a
required amount of drops is also challenging among,
zero gravity.
So the accurate administration of the, drugs by
drops has limitation,
on ground,
maybe as well.
So the,
therefore, we
have to find a solution
how to administer,
the drops, and it should not be in
a fluid state, that it should be in
a solid state.
So, there was the,
motivation for developing
the so called
eye eye insert.
So you decided to create a solid insert
to treat SANS, which is spaceflight associated
neuro ocular syndrome?
So SANS is one of the top five
health problems noticed during space mission.
The occurrence is usually fifty percent after a
few months of, spaceflight.
The rate of vision loss ranges from minor
to, quite,
severe,
problems
where could be also,
caused
so called legal blindness.
And this is very important for the astronauts
because they have to see what they do,
with the computer instrumentation
in spacecraft.
So to address these problems of SANS, the
precise and simple dosing of ophthalmic drugs used
for topical treatments is a key issue.
So, therefore, we saw that we have to
do a solid solution,
which can be soaked by the,
medication like, the, non steroid anti inflammatory,
fluid.
And to insert in the lower lid, of
the eye, it, solves dissolves,
within
a certain time, a certain time span,
and, can be the drug can be released,
and the drug can have the effect, on
the eye
without,
using,
drops.
Okay. So, the device is based on nanofibers.
So what's the role of the nanofibers in
this?
Yes.
It was mentioned by the professor that we
have to make a solid formula
which can contains,
different,
drugs or or active pharmaceutical
in ingredients in the future.
But,
if you want to prepare an eye drop,
it's not too,
hard to to produce because
you have to reach a quite stable solution,
using water and and almost that. So but
to create a solid formula is it's not
easy to do.
And, previously,
we worked a lot with nanofibers,
which means
electrospoon,
nanofibers.
And, it means that we produce these, polymeric
fibers using
electrospinning
technique.
It's a so called electro hydrodynamic
method
to
form solid,
but quite soft,
materials, mattresses, which contains,
like a tissue, like a nonwoven tissue, of
these,
nanofibers.
And, the basic,
concept of this technology
is to make make us a a stable
solution
from your drug candidate
and make a stable solution from your,
basic polymer materials.
After that, you should make a good,
homogen
mixture, from these two component.
And after that,
you can, apply this outer spinning technique,
which means,
rapid
almost immediate,
dryness of this, liquid,
component mixture.
And after that, you can, collect this
dried by but, soft,
nonwoven
scaffolds.
And during this process, this, polymer
change,
which can be found in in in the,
initial precursor mixture
can entrap or encapsulate
the drug component inside
the fibers.
So this,
this process
mean the drug formulation step.
And it's also important to note that,
this polymer chain can encapsulate
small molecular drugs
or macromolecular
drugs or biological
agents
because the shaping,
of these,
components are so flexible.
So this matrix,
will,
be presented
as an institute
formation,
next to the next to the,
drag components.
And the final materials,
we will be a very, very flexible tissue
like,
matrices.
And after that, you have to have to
make
a so called downstream process to to create
the final form, of this tissue.
And in this project, this this was the
the most maybe one of the most, innovative
step how we can form this this,
eye insert to to ensure
the the required geometry,
size, surface properties, physical chemical,
properties, and so on and so on.
So, our innovation,
involve
some existing method,
but finally,
hopefully, you make a brand new mixture of
of the existing method to to create something
new which can be maybe a promising alternative,
for example, to create,
eye disease in in space and, of course,
on the ground as well.
Okay. So, basically, you've got these sort of,
biocompatible
polymers,
and then they are, the drug is is
incorporated into them, and you make them the
correct size and and everything. So
how how long a time period can the
insert deliver drugs? So if you put it
into your eye, can it sort of deliver
over a longer
time period? Because obviously, with eye drops, you
have to do them every few hours,
which Yes. It's
very, very,
interesting and straightforward question because the,
we we we, saw that, this is the
one of the the unique advantages
advantage of nanofibers,
because it's on demand. So, you you can
set up,
the the dissolution properties of this insert
by the selection of
the the good,
type of polymers,
the the structural properties, the morphological,
properties.
For example, the molecular mass of the polymer
is one of the the key properties which
can directly influence this solution,
profile.
So, if you want and if you need,
rapid, dissolution,
you can make
detailed optimization
to find the the good polymer candidate and
good airflow spinning,
conditions.
Or if you need an elongated,
this solution, elongated release of the drug, for
example, to make a much more
extended
therapeutic
window,
you can you can find,
other type of polymer
to to ensure a much slower, dissolution. For
example,
one day,
time frame. So it strongly depend on on
the aims of the final therapeutic application,
but we have the possibility,
to to control this, physical chemical properties,
of of of the drug release. And it's
also very important to know that, okay, we
we know the the,
suitable drug candidate, for example, to treat, the
SANS, symptoms.
But our study on the ISS was,
a very, very important first step,
just to to make a technological demonstration
that this type of drug carrier system can
be a good direction or not. So our
first experience was about to to test and
check,
the applicability of this so called empty,
of the mic insert
which, didn't contain drug.
Only just the the carrier, materials and the
polymeric components because,
of course, you have to have to,
check a lot of official regulation,
stated by our
official governmental
systems
or or has,
offices. And, of course, we have to,
have to pass a lot of safety and
and other test,
which was,
required by the Nasar, Exxon, SLS, and so
on. So
we we have have to,
find the type of polymer,
the applicable
liquids,
the the shape and the other, other parameters
of the insert
to to make,
really,
safe and and and applicable,
drug resistant.
I would I would like to add something
that,
in space,
you might need a long term application of
drugs like the anti inflammatory
drops and, might be also short term, needed,
like antibiotics.
Usually,
during earth conditions, antibiotics should be administered about
three, four times a day. But,
this slow release could be very important for
the non steroidal anti inflammatory
drugs. So,
in the near future, we have to test
that,
which component,
is responsible for
long release and for short release. And in
spacecraft, in long long term,
spacecraft,
astronauts might have conjunctivitis
such,
intraocular pressure elevation,
and so not only macular and sun related
problems.
So I think we we have to prepare
that,
quite many optometic,
drugs should be available on spacecraft.
Okay. And and could the insert be used
to deliver more than one drug?
Yes.
We have a lot of, quite long and
interesting discussion,
with professor and and with our, team.
And,
we have a lot of idea,
what type of,
drugs can be a good candidate to to
treat other disease not only. So we don't
want to focusing,
only on SARS, but other general parameters can
be also caused, during the space vet or,
of course,
in on in the on ground, patient care,
as well.
So, yes, absolutely.
It it was,
a basic,
basic,
requirement
in our team to make,
more or less generally applicable drug delivery system,
which can be applied,
to formulate,
different,
drugs.
Let let me give you one practical example
that,
in,
normal,
patients, glaucoma patients,
there are medication which has two different components.
So,
I think,
on this example,
we have to work on that that,
several,
drugs can be inserted into this insert then
can can have, the effect, among,
zero gravity. So I think this is very
important, and it was a very good question.
So already there are medications in Earth's conditions
with, two or three kind of different, drugs.
So on on this principle, we can, use
this idea also among,
spacecrafts.
Okay. And then my next question is, how
easy is the insert to use?
Yes. It's a good question because it strongly
depends on the on the user, of course.
I I think it's not
more difficult than to apply a simple,
regular contact lens
anyway because, it's it's a very, very small
object.
Yes.
Maybe we can we can use the example
of, for example,
small rice,
piece.
But, it's a very, very,
important difference that our
inserts are so soft and flexible.
And
just have to put this small,
ophthalmic insert manually,
into your lower eyelid.
And after that,
maybe after few blinking,
and after
half or one minute,
you won't
feel,
the veering,
of of of this insert.
And, anyway,
your your
vision,
will be exactly,
the same,
with inserts and without,
inserts,
of course.
And, if if you,
don't,
pull down your,
eyelid,
and other people
won't,
realize
that you wear the insert or not because
it's,
absolutely,
discreet.
So,
I think it's a good good point.
And,
yes, maybe, of course, it needs some training,
because you have to put something into your
eye. So, obviously, you have to practice it.
But, as I know, if you,
go to,
shop land shop and and want to,
be a first
contact lens user, you have to do the
same procedure just to
to to train,
the the application of the lens. So I
think it's it's very similar,
with our, inserts,
as well. It's not more complicated than,
dropping into the eye. It cannot be seen,
and it cannot be fed within a couple
of seconds. So and it dissolves automatically by
itself and releasing,
the drug,
which is incorporated.
So I think it's quite easy to use.
I think also notes,
can make much more difficult tasks.
Yes.
Anyway,
that was one of the first, in the
most important,
questions said that, okay, we have experience
on the ground,
with the natural condition. And,
for example,
the aim of of the study on the
ISS,
is to to explore
the differences in the insert application,
the manually,
the the effect, and and and
the the feelings of the insert viewing,
on on on the ISS. So it's a
very important,
question.
Yeah. So, I mean, I was I was
gonna ask. So, basically,
in very recent Axiom mission four,
these eye inserts were taken to the International
Space Station
for this testing in space,
and the experiment was called ENGSANS.
So, can you tell me a bit more
about what these tests involved?
Yes. So,
because,
you know, it's very, difficult to to involve,
analytical systems,
on on the ISS because, of course, it
has a lot of, limitation.
We wanted to explore,
at the first time that,
just just to collect,
some some extra information about the, insert placing,
insert wearing, how it can, affect
the the simple,
vision properties.
So to to do,
this,
we apply some standardized
questionnaire,
which is,
which is good to to make an objective
information
about the the vision,
properties.
This is the abbreviation of, visual,
sensing,
setup and the ocular surface disease index.
It contains some standardized,
direct question
to measure,
these these, these properties on the wearing, on
the application, and and,
and about the the the division,
properties,
because, you know, it's not easy to tell,
something because it can be so subjective
to
to to describe.
So, we really want to to apply
something standardized and and, and measurable,
a test,
on it.
And, of course,
we we try to try to,
involve
some tests,
with with
OCT measurements to make a comparison
between the prayer and the post flight
condition
of of of the eye.
And, of course, we have other,
tests,
to make this this,
a comparative study,
involving,
some
in vitro and ex vivo
investigation
to to check, for example, the changes in
the physical chemical condition,
the the the dissolution conditions and and other
other properties of the insert. And it's also,
important to note that,
beside the the human,
application,
we,
develop some
API,
so active pharmaceutical ingredients
loaded
insert as as well without human application,
but for material research and and pharmaceutical research
because,
we try to plan the future and and
we have to collect the data and the
information. For example, the drug stability
in in this, solid, drug delivery system
just to to see,
what happens and to make a comparison. For
example,
the same drug,
how how,
we'll be affected
in the zero gravity in a classic conversion
hydrop form or in this,
developed solid nanofibers,
delivery system because
these informations are so essential
to to make a good basic for the
further development.
Okay. So when will the findings of the
experiment
be analyzed and shared, and what what are
you hoping to see? What results are you
looking for?
Yes. I think,
it's it it can be well fitted in
every,
basic and applied research. So but, of course,
we are so motivated
to collect the the results, and we get
every help from the program and the exon
space and the NASA as well. So we
are very grateful because we have very nice
collaboration, and we want to use every effort.
But I think,
maybe
between half and one year,
And after that, we we can collect the
data, make the the,
evaluation of the results, and and after that,
we can release and and and we can
make a quite
informative,
scientific dissemination of of our findings.
So I think we have to emphasize that
it was a short term,
spacecraft,
so about,
two weeks.
And so we were curious that, this new
technology for the developed eyesert,
application,
we performed it without,
drugs,
how it works. So it was a so
called empty nanofibers
eyesert,
with the potential,
to have,
drug
delivery system, not only one, but, multiple drugs
as well,
if it's
important.
And, so the first,
task was to prove
that it works among zero gravity.
And then,
we can start,
other experiments that,
longer
dissociation,
time,
how it works. Because,
hydrox usually,
with conservative
material
and without conservative material.
So we have to know that how it
works with this nanofibre
insert that does it influence the conservation,
the drug delivery
process or
not?
How it's how
stable is it for a longer time? Because,
if there will be a
one year or two years
mission, then, this is, I think, a very
important,
question. So the
final result of this, trip will be analyzed
within half and, one year as Diana
told. And, hopefully,
we can conclude that,
it works, and we can go on,
for further,
application and experiment,
in Earth conditions as well and also among
zero gravity.
Okay. Great. I mean and then so the
technology was developed by researchers at Semmelweis
University
and Budapest
University Technology and Economics.
So what were the roles of these two
different institutions?
And, also, how does the company SpinSplit
fit in with it all?
This,
I think we can say it's a quite
complex,
innovation
task. So,
absolutely, it involves,
two,
quite big and great university,
in Hungary. And that was Semmelweis University
and,
Budapest University of Technology and and Economics,
because,
we can we can
define
well,
the different
innovation
area
regarding,
the clinical and pharmaceutical development
side and regarding the technological
side
because, of course,
we have a lot of,
lot of,
engineering question and and a lot of pharmaceutical
question and medical question.
So anyway,
just from my side that, was,
the most, interesting,
part of this project, how we can collaborate
and and work together.
And,
and and,
for example, to make, the clinical
trials and tests and the pharmaceutical investigations
and and and the material
investigations
as well. We I think we can make
a quite, fruitful
collaboration and and nature of of this,
institute.
And, anyway,
spin split, it's it's
spin off like,
small company of, the University
of Technology and and Economics.
And, SpinSplit
company is the responsible,
on the nanofiber
production the nanofiber,
development.
And we have to, develop,
a very first, first time anyway,
the aseptic
production of nanofibers
because it was a very, very,
hard
requirements of the of this project that, if
you want to, develop an off atomic,
drug, you have to be sterile.
And it's very easy to, to do if
you want to make a simple eye drop.
Because, for example, with the applying of a
sterile filtration, you can manage it and that's
all.
Almost.
But,
we have to have to,
integrate
our technology
on a totally new platform
in in the which means the aseptic,
production.
And,
we could get a lot of very, very
straightforward
information and and vision and approach
in in the final,
development step,
anyway. So SpeedStreet was was the the the
main,
the main head to how we can we
can,
develop this this technology,
on on on the aseptic
production.
I think it's
a very nice combination of translational medicine,
and a cooperation between the technical university and
the medical universities of human studies and the
physical and chemical studies.
And historically,
I, as
a lead ophthalmology in the eye clinic,
were involved
in the pre
examination
of the, astronaut applicants.
And then I looked after
in literature and in everywhere that,
what is the
effect of zero gravity on eye?
And I think it was a very interesting,
realization for me that,
the blood circulation goes upward,
in zero gravity in toward of the head.
And we have a lot of diseases in
earth conditions like diabetes,
then,
macular edema,
in age related macular degeneration,
which resembles in symptoms that what can happen
among zero gravity.
And so we have medication for that. And,
but the medic medication, as I,
told you, explained already at the beginning, that
it's a drop formula.
But it, I also found that that it
doesn't work at all in,
among,
space conditions of zero gravity.
And then we met professor Balog and also
professor Diana,
Weiser Balog and, sat down. And, so my
thought was that we have to find out
some
delivery system which works among,
zero gravity.
And
then they had experience with this technology. I
had experience with atomic,
treatment conditions and, also symptoms and the diagnostics.
And so,
how is it started? This is how is
it started about,
let's say, two years ago. And so, gradually,
we could develop this nanofiber
technology.
And,
so I think, we're on the edge that
it also can be used
for
for some other purposes
among Earth's conditions as well. So it's not
only for
the spacecraft. It it can be used also
among, Earth conditions
for other,
eye diseases and problems. So you have to
have a dedicated ophthalmologist,
a physicist,
and a person with
a chemical and,
pharmaceutical
experiences.
Yeah. And then we all all and we
always,
and continuously,
put our inputs.
So,
I think it was a very, very,
so called classic,
type of of collaboration because
they're always in contact. And then always, if
we have a problem, we always,
discuss it and that everybody put put,
the best for three Yes. Then and and
and the best knowledge to to to solve
it.
And, anyway, we we, can get absolutely,
the maximum,
support for,
from the Hunor, program as well because,
this program has also very,
good experts.
And, we always share our expertise. And and
if we have some problems or limits,
we we can we can manage it and
and and solve it. So,
we are very grateful to the Hunor and
the Axiom, space company, as well because
it was a
a big collaboration
and and and and the hard work
together.
Huna, that's the Hungarian to orbit astronaut program.
Yes. Yes. Yeah. Okay. Cool.
So
just looking to the future, could you sort
of just give an example perhaps of how
the ion
could be used to help astronauts
and also how it could be employed
on Earth more generally in the clinic?
Okay.
I think,
results so far are very promising.
So the application of a solid nonfibrous
insert
could represent
a kind of a straightforward approach to treat
eye disease in space. So,
like, macular edema,
like,
some, edema in other part of the retina,
then swelling,
the optic nerve head, and some,
small,
none really significant, but we can call it
infarct within the retinal,
layer.
So,
by adjusting of the drug release, several treatment
protocols can be achieved. So,
like,
intraocular pressure elevation,
because at the start,
the pressure goes up in the head. Sometimes
the face also
swollen a little bit, and also the eye
pressure might go up. And if it's,
stays for a longer period, like, one or
two weeks, then it's needed to be treated.
So I think in long term release and
combined drug, forms,
can be used in,
in space for long term,
space journey.
So we have to prepare that what kind
of, drugs can be
included into one insert and what,
should be, separately in another insert.
So,
but the rapid action of the proper drugs
has also
unique, advantages.
And so in long term, we can use
it also,
in patients in earth conditions who cannot drop
by themselves, for example, but they could put
the because they have a shaking hands,
for example.
But they could put,
this insert,
much more easily
into the lower lid.
And,
also, there are,
for anesthetic purpose before,
an eye operation,
Also, something for,
dilation of the pupil,
then,
pressure lowering,
then also artificial tear because,
in
air condition
using an air condition, the air is very
dry. So some people needed,
some
artificial tear. Also, when we use a computer
screen, for example,
we measure that we blink
twice
less than no among normal condition. So the
dry eye symptoms among computer users are also
very important. And, also, it could be very
similar
your
space scrub journey. So I think the future
is, hopefully with us,
with with this research team. And,
also, I think NASA and ESA, so the
American and also the European Space Agencies,
found it
quite nice, this idea, and so we can
use it,
among space conditions and also among Earth conditions.
Great. And then finally, my my next final
question is,
what's next in the pipeline
for this project?
Yeah.
Now,
we are in the very interesting
so called post flight,
research period.
So it means the the collection and the
evaluation of, of our data.
And,
hopefully,
we will have a lot of,
feedbacks
and and and discussions,
to to
to draw,
the little bit bigger picture,
of the result,
of this
project work.
And, of course, in parallel,
the the data,
explanation,
we have, already started to,
to to, prepare,
the further steps,
which means,
how we can,
encapsulate,
different,
drugs,
in the developed,
nanofiber,
based, delivery,
system.
But it's, important to highlight that it's require
a lot of paperwork
and and a lot of, you know, preparation,
to get,
the proper permissions
and license fees and and and other other,
documentation.
So it takes very,
long time and and and,
bigger for
but we we wanted to
turn in
in in in the future,
our
results,
which can, be get from from the ISS
of of the Axiom four, mission,
and we wanted to integrate this experience,
to continue,
this work.
And we want to identify
the key parameters,
of the insert development.
For example,
further optimization
regarding the
geometry,
the shape,
the surface properties, and and other other,
other,
parameters
of of the insert.
And and, it's a very interesting period because,
maybe
we can make
an existed, but maybe a new approach,
how we can make this further development
because we have a lot of additional information.
For example,
the the space conditions
and and we,
have results from the clinical investigation
as well.
So it's a very nice task
to make a good and straightforward mixture
from from this result and and and to
make a good basis for the further development.
I think the physical and chemical analysis and
also that how, this insert behaves,
in Earth condition with,
drug and without drug, very important.
And so in the future, we have to
find out that,
one drug,
multiple drug administration,
is the better,
how it really works
with, normal
humans, not
only astronauts.
And then we can also use it,
among zero gravity.
And,
hopefully,
all experiments can be finished and concluded
until the, long term
spacecraft
journey starts within couple of years. So I
would
summarize,
like this. So we go on this path,
and, hopefully,
there will be some,
very new things which can be used and
can be favorable for,
patients in Earth, so among normal conditions and
also among zero gravity conditions.
Excellent. Well, thank you, Zoltan and Diana, for
speaking with us today.
Thank you very much the opportunity.
I do. Clear.
It was so interesting to talk about our
project.
Thank you.
That was Physics World's Tammy Freeman in conversation
with Diana
Balog Weiser of SpinSplit
and Budapest
University
of Technology
and Economics
and Zoltan Nagy of Semmelweis University.
Thanks to Tammy,
Zoltan, and Diana for a fascinating discussion.
And a special thanks to our producer, Fred
Isles.
We'll be back again next week.