Science on surfaces - Tips, Tricks and Tools
Science on surfaces - Tips, Tricks and Tools
20. Nanomedicines – overcoming drug delivery challenges by intricate design
What are nanomedicines? And how are they different from traditional ones?
In this episode of Science on surfaces we talk to Dr. Gustav Emilsson about the fascinating area of nanomedicines. Dr. Emilsson is working as a Postdoc with nanomedicine development at the department of Advanced drug delivery in Pharmaceutical Science at AstraZeneca, a global, science-led biopharmaceutical company.
We start out by talking about what nanomedicines are and how they work. Dr. Emilsson explains how the intricate design of these minuscule drug carriers can help overcome challenges such as drug toxicity and solubility issues, and how nanomedicines can be used to control the drug release in the body. We also talk about a phenomenon that is very relevant in the context of nanomedicines - the formation of the so-called protein corona, which affects how the drug delivery vessel interacts with the body. And finally, Dr. Emilsson shares some thoughts on what the future looks like for this intriguing area.
Thanks for listening! If you are interested in surface and interface science and related topics, you should check out our blog - the Surface Science blog
Surfaces.
Speaker 2:So welcome to this podcast today. We will talk about Nanomedicines and we will talk about what Nanomedicines are and how they differ from traditional medicines. So today's guest is Dr.[inaudible] and Gustavo is working as a postdoc with nanomedicine development at the departments of advanced drug delivery and pharmaceutical science at AstraZenica, which is a global science led pharmaceutical company. So welcome Gusto.
Speaker 1:Thank you very much.
Speaker 2:Great to have you here and to learn more about this exciting topic. So, um, could you just start with the basics of what's anonym medicine? Yes.
Speaker 1:Okay. So the basics or my, my view of all the basics is that anonymous and it's something that is, uh, it has one dimension, at least in the nanoscale range. So you have either like, uh, I mean, when you have some sort of particle or, or, uh, how to say call it able to have one diamond between one and 100 centimeters and in, or it will have, uh, at least it will show properties that are, that are related to its size. And even if it's, sometimes it might have a dimension that is maybe above nanometers, or it could be a micro meter, but it still shows properties that this, uh, related to, to it's size 12 to two nanometers size. Um, and it is composed of, uh, yeah, many different things. So like anything that you can actually make into a nano-sized object, you perhaps use as some sort of medicine or a sort of a container for a medicine in that case.
Speaker 2:Hmm. But if you take the, I mean, if you compare it to what we would call like a traditional drug or medicine, those could also be in the nanoscale, I guess. So you would have an active molecule that would also be in the nanoscale, but that wouldn't qualify as a nano medicine.
Speaker 1:Yeah. Yeah. I think it's a difficult definition. I think the definition is still a bit, there's not a single one definition. I think there's a, there's a room for interpretation probably, but I think that the many thing, many people think that it is some sort of, I mean, you, you, you, you have done something, it's not just one molecule, usually it's like, you're, you're doing some sort of a complexation or you're mixing different things to create some sort of new area, maybe. So you, it's not just one thing, but usually like that you have either remind that container and then you feel this, or whatever with some sort of drug or that you have, I would say that it's composed of more than one, uh, component that list. So
Speaker 2:It's, uh, it's like, uh, more of a complex design, a carrier with a more complex design than just one single molecule,
Speaker 1:I think in general. Yes. That it can be, I mean, it can, it can also be that there is a, it's a non nanoparticle in a certain size range. And then depending on what you want to get, maybe that's like, it's another particle made up, so some sort of material. And of course that material could also be found as a, like a, like a soul or something. But now we made to do like a certain shape or a size range that is suitable for what we want to do with it. Yeah.
Speaker 2:Okay. So what is the special with this category of medicines?
Speaker 1:Yeah, I think what is special is that you can try to, when you make it into this size range, you can see it. And like you can gain new properties. You can gain new ways of working with medicines. Like, uh, for example, there has been recently quite approved drugs that where you have, uh, like, uh, you have a complainant in this case, like a liposome and inside of this type of zone, you can then have like a combination of drugs. So you, you don't just have one drug, but you have like a cocktail of two drugs.
Speaker 2:And what is like the song for those who don't
Speaker 1:Know? Yes. A liposome is a, uh, it's a liquid, the in case, the volume of, of, of a liquid. Uh, so you have this life and then they, they have like a shell then in the inside, it could be filled with some liquid than the, and it's sort of a similar to what you would find in cells. You have like this liquid, the tales, and then, then you have a hydrophilic and hydrophobic, and then they create this lipid bi-layer that will then enclose into like a sort of spherical form. And they will have a liquid inside and liquid outside.
Speaker 2:It's just like a, it's a spherical container that you can feel with.
Speaker 1:Yes, yes. Yeah, exactly. It's good to contain something. And then in this, for example, some recent, I mean, it is, and it's quite prominent that we're saying in the, what you would call Nana medicine, there's a lot of lyposomal, uh, drugs being investigated. And also some that have been improved, like approved. And I mean, when you, when you put something in a container, you can then make sure that what you have inside area's system. I mean, you can find new things that like, say that, you know, that, or you find out that if we deliver these two drugs at the same time or at a certain ratio, and they have to be delivered like within a certain timeframe or a, or they have maybe different characteristic that makes it impossible to do it. If they are not in the same container, then you can then for example, use this sort of containers where you put them in nicotine, and then wherever the container goes, when it's released the, it will be released at the same time, then you can probably gain new, uh, effects that you will not be able to do with just injecting these two things at the same time.
Speaker 2:So it's, um, it's a way to both package drug molecules and deliver them to a specific site. Yeah. Okay. And what did you say about, so they haven't now they've had them used to mixed of different molecules in the, in the liposome or in the vesicle. Is that something that is new or is this,
Speaker 1:I think it's quite new and it, it was, uh, it was approved by the FDA for, I think three years ago. And I'm not, I'm not sure. I think it was one of the first, uh, where they showed that this concept, when you actually take two, two different drugs and you have them in the same, uh, containers, we'll see. And then when they are code delivered, then they have, uh, increased the efficiency. Uh, and, uh, it can also then on this increase than lease that you can have like a, you, you just need a lower dose compared to if they would not be delivered at the same time often what you want to achieve. You want to sort of, I mean, in a perfect world, you would inject an animated thing and it would only go to the place where you wanted. Uh, and then you would be able to, if you couldn't get a local concentration where you wanted, for example, in, in, in a certain Oregon, and then you could reduce the amount of drug that you would inject compared to just injecting it by itself. And then you can avoid certain toxic effects and, uh, going to increase the range lower. I think you can change sort of the way that we deliver.
Speaker 2:Okay. So how do you, how do you make it go to just the, to where you want them?
Speaker 1:Yeah, I think that's still a debate if you can, but you can, at least now you can see that th th there will be, usually there will be a difference if you just have the, the, the medicine or the drug or whatever you wanna call it. Uh, and you inject that, then you will have it distributed in a certain way. And then if you have it encapsulated in something, it will most likely to distribute in a different way. And if this system, the way that you would want it to, then, then it can be beneficial. And, um, there's also people looking into using different, like targeted in ligand so that you can actually modify this USA. For example, the life was money modified the outer layer with something that will buy into a certain receptor. Uh, you can then hopefully get that to bind in an even higher degree to where you want it and less to the other area.
Speaker 2:So Lygen is a molecule that you basically put on top of the membrane, or how would you explain that?
Speaker 1:Uh, I would explain it to, yeah, it is. I would explain it that it's, it's something that you, for example, if you have a cell and this cell has certain receptors, it it's a certain proteins that are sticking out or dismembering. And then, uh, you know, or you find out that if you, you can design something that binds to one of these receptors, and then you put the thing that binds the receptor on the outside, or on the surface of your carrier, then hopefully it will interact with this receptor and stay there and maybe also get internalized. So it could take in by sales and then you can deliver your cargo to where you want it to be. And then of course, if there are different cells and some cells might have this receptor in a higher abundance than others, you can use this as a way to try to target or get more on what you want to do, where you want.
Speaker 2:And this works today.
Speaker 1:Uh, I don't know if it actually, I think it's debated the weather ever on a, I think this is like the dream. So you would, you like in a perfect world, you would have a, you would have a carrier and it would be modified in such a way that it would only bind to a certain place. And then when you inject it, it only goes to them. But in reality in Korea, it's something that still we're striving for. But I think that that's the, that would be the ideal goal to have it only go to one place, but of course it's very difficult and challenging.
Speaker 2:Hmm. So, um, you mentioned that you could use a liposome as a carrier. Are there, are there materials that you could use as well or other packages that you could use to transport the drugs?
Speaker 1:Yes. There are. Uh, there are quite a few. I mean, there are, I mean, when you think about the carrier, it could be that the carrier could either be like a liposome or it could be some sort of polar Merrick, uh, carrier or shell. There's also something called[inaudible], which are quite small than, than, than, than you're actually like binding the drug. I mean, it's quite a wide range. Even if we are in nanoscience range, we can have something that is maybe five nanometers, or we can have something that is 100 nanometers, which is still, if you just look at that scale, it's quite a big difference working with them. They're totally different. But the goal is the same. And I mean, there's polo American. You can have a protein bound particles. For example, you can use is the definition is quite wide, what is a carrier, but in somehow you can modify your material with something that enhance it or changes its properties. You have a, for example, a drug nanocrystals, which I've also been working with. Uh, and, and then you have, uh, certain cases where you, where you actually modified the surface of these with, with the protein.
Speaker 2:So what does the drug town of crystal or what is, I mean, how
Speaker 1:A drug, not a crystal is an a, a, is a drug that has been crystallized. So it's, it's compostable surely the active compound that you want to deliver. It's a small molecule call it, and then this can then be made into like a nano-sized crystal, let's say.
Speaker 2:Um, so there was no rapping outside of this.
Speaker 1:There is not, uh, as extensive as the container, if you could say that you have something on the surface to stabilize it, um, I don't know if I would call it a container. I would say it's more like a, yeah, some sort of shelves maybe, but if it's not like it's less that you have it in, in this case, the drug itself is what is the nano, and then you have to change the properties of the surface. Uh, traditionally this is done for poorly soluble drugs. You can have something that is, you find out that it is very active, or it would probably bind to where you want it, but it's very poorly soluble. So if you give it to someone, it will dissolve at such a slow rate, uh, uh, that they will not be really feasible to use it. And then if you make it into a smaller size, then the dissolution rate will increase and you will, will actually reduce. And then they can also then be combined with sometimes different solubilizing agents or oils or, and these, then the problem can be that maybe the substance that you give it, it's not, it's not what is the most toxic, but actually what you are using to solubilize. It might be the toxic component.
Speaker 2:So you said that you make it into a smaller size and that makes it more soluble.
Speaker 1:Um, yes. As smaller compared to, if you would think about it as a powder that you usually, you might, this might be in the micro range, and then when you make it smaller, you make it into what is nine on that. So,
Speaker 2:Okay. But you, in the end, you want it to be like single molecules, I guess. Yeah, yeah.
Speaker 1:Yeah.
Speaker 2:So you pack those molecules that are the active substance into something bigger, which is a crystal. And then that will dissolve in the end or yeah,
Speaker 1:You have the small molecules and when, and then people are people that notice things that they, they don't have the crystal license, you can make this small molecule into crystal, sort of like, if you think about, uh, like that, when you make a crystal for a x-ray crystallography, then you have a, like a protein that you can manage to make it the crystal, but you can also then manage to make a small molecule into crystal. And this crystal can then later be the, this crystal can then be big. It could be micron size store or launch, then it's too big. So then you try minimize it by either mechanically grinding it down or, or, or producing it in such a way that it actually becomes a nanoscience okay. But in the end it will dissolve. And then when it solves, it will be what you have is this small molecules.
Speaker 2:So you tailor the size of this crystal. How do you decide how big the crystal should be then? Or do you want to make it as small as possible?
Speaker 1:Yeah, I think if you just want to do to solve the fast, you would want it to be as small as possible, but it's, uh, I think it's always a compromise between you want it to also be stabilized, but what you have produced would not change over time. So I might say that you make it very small and you will notice that it somehow hence to increase in size. Maybe it's better to make it not as small, but it's somehow I think it also difficult to, to, uh, I would say click control exactly what size you can.
Speaker 2:Hmm. When you say get bigger, they would aggregate then, or how would they get bigger? Yeah.
Speaker 1:Maybe aggregate to go, or it, depending, I guess if you make it into a stable crystal nano crystal it's should not aggravate it should be that size. But I think in general, if you just want it to dissolve faster, you would smaller the better, but the, it will be what we call a nano suspension. So you will have these crystals then suspended in a liquid medium, and then each crystal will be stabilized by something on the surface that prevents them from aggregating and they, something can be all immerse or protein source.
Speaker 2:And, and what you put on the surface will not prevent them from dissolving later in the body.
Speaker 1:No, but the, no, I mean, you, maybe you could create the shell that is so thick or impenetrable that it would, but, uh, I think that would also be interesting as a technique, if you could do that, that would be of course, interesting that you could, if you would, could find you in this shell, then you could maybe control the dissolution rate in there in a very precise manner.
Speaker 2:Um, so what, what is then the benefits of the nano crystal effect compared to just taking those smaller cubes and putting them inside a vesicle and deliver that with a vesicle instead?
Speaker 1:Uh, I think the, the benefit here is that you have quite a lot to say yeah, sort of simple system, because it's traditionally, when you, from my understanding, when you want a drug to be approved by certain organizations, then you go through all the steps and the less complex of a formulation you have. I mean, the less things that you have to check[inaudible] since you are your drug delivery or your, your nano object is made of pure drug, you are removing a lot of components. And so if you have an automative life or something, then you also have to check all of these things. Like, I mean, then you have something inside, but maybe you even, I mean, you have more components that are not a drug than what is the drug and you in the liposome, you will not reach the same drug loading as a crystal. Crystal is composed of 100% of this molecule. So it has, you cannot be achieved a higher drug loading in the life of some, I'm not sure what you would get, but it's gonna not be 100% we should have, because it will be fully a liquid container with these molecules.
Speaker 2:Right. So more complicated to predict the exact behavior of all the parts of our liposome carrier, then
Speaker 1:ASM, maybe more characterizations that has to be done and show different agencies to show it working. Like you have to show, I guess that each component is stable, not breaking down, but if you have fewer components, less things that you have to check on.
Speaker 2:Hmm. Okay. So I'm thinking a bit more about the design. So what, what parameters can you vary in this nano medicine design? You've mentioned that the contents and the coating and the wrapping and molecules on top, and it seems like it can vary many different things and really get a very intricate design in the end.
Speaker 1:Yes. I think this is both the average and also the challenge because you have a lot of parameters that you can vary. I mean, as Susan, we can't wait into size, we'll help them where we can better to surface chemistry, which we, I mean, my background is sort of surface background. So, uh, I mean, when I think about it, that's the problem. Of course, everything that is that is that you will be indexed as some sort of Portugal will, will be, uh, interface. You have some sort of interface that will, that will be recognized by, by the body or, or in somehow. And, uh, of course the newer, when you make the accounting to nanoscience, then you are increasing the area per volume. So you have compared to micro-sites, you have the importance of the surface becomes more important. So you have to be really like, you can tailor it and hopefully the surface chemistry in order, then the shortage or, or the, um, like what was more like, like what, what type of polymers are put on the surface or what kind of properties are underserved? And then once these go into the body, then they will start to accumulate proteins and you will, you will get like a, I would say, biological profile for them, maybe which proteins they with. And of course, then it's a very like layer complex problem.
Speaker 2:So this is the, the protein Corona you were talking. Yes. So could you describe that a bit more? Cause I, I that's, that's a kind of, uh, like a challenge to handle. If I understand correctly that you will always get this accumulation of proteins or possibly other molecules as well. I don't know, on the surface, when you, when you insert the drug into the body or any nano sized object or any foreign object, maybe even in the body, you will have an accumulation on the surface proteins, right?
Speaker 1:Yes. Yeah. Uh, I'm not an expert in this area, but, but from my understanding that that's exactly what it is. It's like you, anything that is interested in what they will most likely and so proteins, and then which type of ordinance that will depend on the, the surface of this, I would say the surface of this particle, that is what is facing the solution, right? So if you have a surface and you have something inside and what is on the surface should be in the main component. And then, then that determines this Corona formation. And this will also maybe change over time that you have at the beginning, you have a certain proteins absorbing, and then they are exchanged or end. And in the end you might get this on stable Corona. But I think this is like a dynamic process. So finding out exactly what proteins and why. I mean, I think you can, a lot of people now, they, they, we can find out like you can do this experiment and you can show that these products are the ones that bind. But then the question is why, why are they binding? It's, it's very difficult to figure out what is the implication, if you have this protein X on the surface and what will that lead to India?
Speaker 2:Hmm. So is there some way that you can prevent proteins from blinding?
Speaker 1:Yeah. I mean, this is also from my experience. I mean, uh, I mean, usually polymers or hydrophilic layer on, on the surface of if this, uh, if you look at like polymer theory or whatever you want to call it, then, then it's suggest that if you can create a dense enough layer of polymer chains on top of it, a surface, uh, then it should be in principle a, uh, a barrier for, for entry of protein. So if you have a dense enough layer or a thick enough layer, it will prevent adoption of proteins. Uh, under then, I mean, in theory, you are usually thinking of proteins as a, some sort of sphere or road, and then you try to calculate this. And, and of course it's an approximation, but it's still tried to show that if you have this hydrophilic like a brush in order to actually reach the surface, then the order, the protein would have to compress this, this polymer and the compressing, this polymer is not favorable because if you have a polymer chains that are very, they are very close to each other, they are so close that they cannot really pack it. Like they would like to be like a shame, any chain or like a string. It would look like to be in any, all over the place. They will not want to be like a straight line because that's not, that's not the anthropic being favorite way, but if you have managed to pack them in such a way that they are in this string, like way, uh, then they would not want to be any closer to each other. So when the proteins rice approach, and then as to make them sort of move even closer to each other, that will be then like a repulsive, like a spring to try to prevent them. And I think it's, uh, I mean, I'm not sure it's, it's difficult to say. I mean, there's a, there's a lot of people doing surfaces that are quite resistant to the proteins. Uh, then, um, I mean, that's where I come from in the beginning, but then you have another world sort of like where we talk about that it's always grown up forming and that, I think it's, uh, I mean, it's difficult to know what is true because it's maybe what we do in sometimes in surface science, then we have a perfect surface and we can clean it and we can make sure that it is, it is a perfect surface, but when you work with nano particles, it might be, uh, I mean, th this polymer might not be as dense as you can do on a surface. You might be able to achieve much higher densities, uh, and different other way. I mean, a very pure surface. This might not be possible.
Speaker 2:Yeah, exactly. So would you, I'm thinking, would you have both this, uh, the polymer brush and like, and that will target the donor medicines? I mean, could they be combined or would you have to go for one or the other
Speaker 1:And you could have, you could have a polymer brush, shorter polymer layer, and then ideally you would have a disliking and wouldn't be on some polymer machine that is sticking out slightly longer. I would at least suggest that because if, if it's otherwise it's might be less accessible. So you would prefer maybe we want to lag and to be protruding, or like at a further and goes on to say, this is what people want to do. I mean, because you want the, if you don't, if you have nothing, like if you have no polymer or stabilization of the particle, then they will not be very long lived in the circulation. So you have to have something on this surface to prevent the particles from actually being removed by the, uh, by the body because they are foreign. So they should not really want to be there, or they shouldn't be there.
Speaker 2:Okay. So they will be removed by the, uh, immune system or something, or, or what happened
Speaker 1:Is this clearance, or if you inject nanoparticles, there's a clearance of them. And then depending on there's papers, showing that, depending on, for example, how much polymer you attach to the surface, then you would have a faster or slower clearance. And then exactly where this threshold is, of course the same, because it depends on what type of particles you have. And, but you will have probably some threshold where if you are above a certain limit for particles will have a substantially longer circulation time compared to if you're below this threshold. Um, and then there's this stress. I mean, it's still sort of like a clearance when we talk about clearance. It's, it's mainly like the liver, maybe on the spleen and different organs in the body that are responsible for keeping us safe or healthy. We want to want to call it. And of course, if something is foreign and this will be recognized and taken up by, by these organs, trying to clear it out.
Speaker 2:Okay. Yeah. So there are quite many challenges here, I would say. So are there any specific diseases these are most suitable to treat, or could it be any type of disease you would use this?
Speaker 1:Hmm. I think that they are opening up the landscape for maybe diseases that have not been previously. You could not treat them. You can have a recent examples of the SSI RNA. So a nucleic acid, uh, delivered, uh, it is possible to treat like a hereditary disease that has not been possible previously. And this is then done by because you then package this, this nucleic acid, uh, in a container and this packing on this. I mean, the container is both like a way to deliver, but it's also a way to protect whatever you want to live. So in case of this nucleic acids, then they are quite prone to degradation. If you would just inject it, eh, it would degrade by different RNs or, or, or things found in your body that wants to break it down. But if you pack it into, uh, a particle, this particle that can protect it from being degraded. So it actually enables them, uh, certain, uh, maybe nucleic acid type of drugs. I mean, this one recently was for, uh, uh, it was sir, and a, so it's, uh, as a small interfering RNA, it tries to lower the amount of, of, uh, uh, proteins produced. And this was recently, there was one called, uh, one bathroom. It was approved, uh, two years ago. And it's, its role is done to actually lower the, the amount of a certain protein that is produced. And because there's protein, uh, one is, is produced in someone who has this hereditary disease. It is produced in maybe higher levels, or it has a mutation that causes problems. And this production then leads to aggregation of these proteins in this person's, uh, yeah. System, which leads to different, uh, problems. And in Sweden, we, we it's called Quicken. Uh, no, but it is like a hereditary disease and it's not, I mean, it, maybe not the, the, I would say biggest moral, but it is a very specialized, uh, treatment. And it has, I mean, so I think that another mannequin provides new ways, uh, to work with certain types of, uh, drugs or medicines that have not been possible previously, you were opening up like, uh, an area, which is, has previously been untreatable, maybe, uh, making it treatable.
Speaker 2:Mm, okay. So, um, I mean, considering all the, uh, the different challenge challenges that you would have to overcome making this, I mean, I guess there's, there should be like a, a big reward to, to develop it and sell it, I guess, and to treat something that is previously incurable would be of course, a good day. I mean, good motivation for it. Uh, and you said that this was approved two years ago or something.
Speaker 1:I think it was two years ago if I'm not mistaken, uh, in 2018.
Speaker 2:Yeah. So there are quite a number of these already in the market or,
Speaker 1:Uh, from a recent review. And as I read them, then they say that there's a, roughly 50 or more, um, formulations currently in the market that are sort of in the nano area. And then there are more than 400 ongoing clinical trials. There's a lot of research going in, but of course all of them will make it, but there's a lot of A-list I think hopes. And then maybe, I mean, since one has, if this, this two years ago now it was approved, it opens up that maybe more might be approved and you'll see that there's actually a can, because this is based on nucleic acids. So you're trying to prevent the production of something in this person's body. And then if you would know that you have, for example, another disease that is also causing, like, you know, that you have problems because you have overproduction, or you have a production of certain proteins, then in principle, at least if you know how to shut down one thing, if you can then just deliver this, uh, another, uh, nucleic acid that then binds to, to this other gene in that place, you could maybe shut down the production of different proteins. So this opens up like a way to, to actually regulate or try to cure or treat at least these diseases that the, uh,
Speaker 2:So you're saying that one would then reuse the packaging and the coatings and all those different things in the intricate design, but then replace what's inside, like the active molecule inside the carrier, or
Speaker 1:That would be the ideal case. I mean, it will probably not work for all because it's, I mean, for if they are similar enough, uh, it might work. Um, but then in the end, it comes down to also where they have to be having this case in, in, in, uh, in the case of this one that I talked about, then, then it was, this protein was primarily made in the liver. So you have to get these particles down to deliver. And I mean, the liver in itself will human like particles. And there's one of thing that you might, might want, if you want it to go somewhere else on the liver, you would want it to avoid going there. Uh, so it's, it's also, it's not just, I mean, one challenge. I mean, hopefully you can then package it in the same way. And then in the end, if you want it to go somewhere else, then deliver, it would have to also face that challenge.
Speaker 2:Mm. But I'm thinking, because you mentioned there are so many parameters that you can tweak and change in terms of like the whole design of this novel medicine. So I was thinking that maybe if you could come up with, you know, 10 different combinations of designs or something, and they could be reused as carriers for, for lots of different drugs or how many, I mean, to, to behave in a certain way, you know, to be clear, like in the same location and all the things that you would like to obtain, and, and maybe then it would be easier to characterize and to get that approved if sort of the carrier design had already been approved. But I don't know if it's that straightforward to just reuse something that you've gotten approved before, but
Speaker 1:I dunno, I directly, I mean, I'm not really, uh, fully into the regulatory part of this study, but it's, from my understanding, it's still a little, very complicated to get something approved, but I mean, the more things like, yeah, that rude, I am assuming that it will pave the way for, for, uh, or similar at least, uh, treatments. So if you, for example, lyposomal, I mean, there's quite a few of the life of someone once. And I, I guess there that they are in somehow quite seminar because you have, at least you have this life, so it can of course maybe be of different lipids or something, but it's in the end, they have to sort of, I think you have to. Yeah. But I think there's also that there's a new sort of landscape for approval. So you have to be it's, I think it's from both ways, you're like, you don't really know what they will, it will be asked of you in what kind of characterization you are supposed to give them, uh, in order for it to, reapprove such a way.
Speaker 2:Right. So that's a challenge. Are there any other challenges related to this in terms of, in developing and getting through approval and get it out?
Speaker 1:Uh, I think it's still, uh, a lot of challenges for example, that this, there's still a large portion of what you inject that actually doesn't end up where you want it, even if you're changing that it doesn't go in the same way as the free molecule or drug. It still has some sort of a preference for certain organs, maybe, but it's clearly in high, like in the liver, for example. And I think this is still a, I mean, of course you would want it to, if you don't want it to go to the liver, you will want to DM it to make sure that it doesn't go there. And I think that's a challenge because it's a, it's a, I mean, if you think about like evolution or, or in a human body or animals in general, we have evolved to, to try to avoid the different foreign things hurting us. And then of course we have developed some sort of way to handle all these things. And then, then when we are actually doing here in the nanoscale, the, these are in the same range as like a virus or something. So we have, might have like a very efficient way to remove things because we have to Gen-Z or things that we know would be harmful for us. Now we are trying to be in the same sort of ballpark as those things that the body has tried to avoid them. It's a very, it's a very complicated, I mean, it could also be, you know, variations from everyone, even if everyone looks exactly the same on that side, it might be awesome. Like personally, I mean, personalized medicine or not, you have to think about like each person.
Speaker 2:So, so you're saying in theory it could be that it works a particular nanomedicine works better in one individual than in another, because their immune system differs.
Speaker 1:I wouldn't exclude possibly possibility though. Yes. Then I also think you think about it it's alone. Yeah. I think people are thinking that it's quite a long way. I mean, the liposomes were first, like from, from, from the first like invention or whatever you want to call it of liposomes was sort of, it took around 30 years to actually get the first lyposomal drug on the market. I think the first one that left on or in the U S was approved was in 1995 and around 30 years prior to that was like when, when life was on, started with the calm thing, I guess. And then, so you have the like 30 years of research going into, or different ways of understanding just this life. And then of course making the actual drug, isn't a totally different thing as well. But I mean, if everything takes time and if we have a new carrier, maybe we would have to be realistic and think that, okay, maybe 30 years is not unreasonable to think that the like, and of course we are, we are seeing approval of new types of amendments is I think that there's still so large potential, but there's still a lot of things that would have to be, I mean, you always want more understanding, like, even if you can get something approved, it could be possible to make it maybe even better, if you would know the things that you don't know today, just continuous improvement.
Speaker 2:Of course. Yeah. I mean, I can just, I mean, it's difficult to, to maybe characterize how it behaves in the body and get an understanding of that. But then I'm also thinking my challenges of, you know, manufacturing, small entities that are with such an intricate design and have them be stable over time so that you can store them and know that they still behave, that they're supposed to in a year or however long the shelf life is supposed to be. I mean, there are so many tricky aspects here that I can, I mean, of course they are included in the characterization and before the approval, but still, yeah. Yeah.
Speaker 1:I think you're right. I mean, there's a couple of let you in academia or think about that. Maybe you develop a new way to create an article, but then in reality, it could be that this way, maybe it's not really possible to scale up. So if you want to do it in other industrial scale, uh, I mean, okay, maybe in the, in the lab, somewhere in the universities, it's fine to create a few microliters, but when you want to start creating milliliters or liters of the same thing, maybe you have to think about is this actually feasible to do in a timeframe that this actually, uh, yeah, so it's, it's a lot of like scaling up shelters of course exists. And I think that's the pharmaceutical companies probably struggled with and trying to create a new way. So,
Speaker 2:But, uh, it's, it's still sounds like this it's still, I mean, it will continue, uh, I mean, it's not an area that will sort of die out, even though all the, like the challenges it's, I mean, it's here to stay and will keep working with it sounds like, right?
Speaker 1:Yeah, I think so. I mean, yeah, you always want to, I mean, science always tried to push for one month. You will love this one day I say, stop and say, no, we are, we are satisfied with we have today.
Speaker 2:No
Speaker 1:People won't always want something. Like if you can cure disease X, you don't want to cure disease Y and so on. So there will always be a continuous struggle. And I think for, for improvement of what we know today, and, and I think at least in my view, even if there's, are there challenges, of course there's still a lot of potential that overcomes possibly the cells. I don't see. I mean, I guess it could be a definition if there's something else that those about. I mean, I think right now there's shown promise for a certain, like, I mean, the field of sort of delivering biologics or nucleic acids or proteins that are also showing promise with these nano sized carriers and that it's also, you're starting, I would say.
Speaker 2:Hmm. Okay. Yeah. So I think, uh, that's what we wanted to cover in this episode. Um, very fascinating area, I think, and really looking forward to what we will be seeing with the next, within the next 30 years, then we'll make some progress. Um, so thank you so much for listening to this episode, uh, with[inaudible] and Dr. Gustavo, Amazon AstraZeneca. And I would also like to take the opportunities to mention to those who are listening or watching that if you're interested in surface science and related topics, you should check out our blog, the surface science book. Thank you.