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, 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.

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.