polymers
So there's some context in terms of how we discuss those questions. Otherwise, we can have a quick session at the end as well and you can ask the questions. But do feel free to put any questions in the chat as we go along and I'll try and answer those as you go. I'm gonna be looking at some basic polling country today, and then tomorrow we're gonna be looking at implants, different types of OK. So hopefully you can all hear me clearly. You can also do presentation. If you can't then let me know in the chat. Let's make a start. OK. So today we're talking about some basic polar chemistry and in particular we're going to be looking at these three areas. So by the end of this lecture, hopefully you should get out of these fundamental questions about So what is it that distinguishes the corner? What's the difference between polymer and a small model? What chemical properties or the polymer controls its physical properties? Finally, how can we modify those properties and make polymers and materials more useful? Most of you know what polymers already are, and you might also refer to them as plastics. That's more that sort of general way that people that aren't scientists might just want. Every day you come across plastics and use plastic all the time. In fact, pretty much everything you do involves some sort of plastic. But they call me a plastic it's basically a very large module umm as opposed to a very small comes from Rick to police mean many and then murdering tasks so many parts and so single parts. So we make polynomial start with these levels and then we clearize them to form a polymer and that's showing the schematic on the slide so you can see we start with these units. We clear eyes will join us together and we end up laying on the chain to join us all of these years, you know so we go to one of us polymers. Why the demonization process? And obviously have two different types of, we're not going to details of different optimization, but we'll say this one here is an example of an addition or step recommendation. So chain recognition. The problem here is an example step recommendation that's not too important here is that looking at form and also having represent that. Some of these top steam, you can see that we started around. One of the units in this case is that through chamber optimization that leads to this plumeric material we've got repeating. So we look at the post, stuff like this refer to it as an extended structure. Now if you join 100, then you can draw out 100 more units or join together. We take a long time and therefore what we do is we actually convince the drawing. And we're keeping the structure and that's showing right here. So repeat unit structure just shows the individual repeat unit which is derived from the one unit and that's inside square brackets. We subscript in that refers to any number of the pigs. So if we start off with 100 more units, we can realize all 100 then theory we can form a format that has 100. Here is that we refer to the continuous. So in this case it's that hydrocarbon chain and we also have pendulums. So in this case those groups come off backbone I know as pendulums. So backbone we have pendant. The one theme is an example of Stephen once again we formulate form the chain and we can use the same, we can draw extinct form structure. Obviously that will take a very long. So those square brackets are encompassing a single repeat unit of that on the chain. And once again the first one in this particular corner we can see that we have a polypeptide background, so very much like a protein or peptide and of that polypeptide that one we have these. What's the privilege? So those are pending to pull the methods. There's there's also other links to be used and we'll talk about things like English and architecture that won't go into that in detail as much. So Paul is going to be classified as Tibetan. So he's a man made for this or natural bipolar. Umm. So these are polymers that pretty much fundamental to all bilateral law. So it's a physical form is pretty much every material product that you use in everyday life. It's not a computer. Now watching this, then that computer is going to have over at least 1020 different types of formulas that make up you're using a mouse, that's a different folder. You've got a pen in your hand once again. So pretty much everything you do involves you go to kitchen to make that coffee, pretty sure your house and corner components. So really we become very reliant as a society on sympathetic course. Now most of these performers are actually derived from fossil fuels that we use are derived from. Obviously that's a problem and there is a general shift towards more. Genetically derived from natural cellulose and that's going to be a long process to Swiss tree natural and renewable disabled sources. So today I'm going to focus on syntheticness. Obviously should be aware that natural bipolar, these are the ones that generated by all the organisms are fundamental to their function, the structure and the function. We're going to talk about things like proteins, peptides and of course. On DNA, so the polysaccharides, the natural polysaccharides give structure, umm, to that volatile Organism. Things like proteins and peptides give enzymatic function or transport function. So for example they could be involved in television or transporting function around the body. And of course like DNA carrying genetic information. So natural problems are extremely important and really life every night will exist. The reason we're kind of looking Chapter 2 Ch 2 and ethylene is a gas that ring temperature. In fact the melting point is extremely Celsius. So if the molecule is really reasonable, you can see that it's less than a noun if you can pay that deployment. So if you take that link and. So this particular example you can see that we formed polyethylene is now the little weight polyethylene has jumped from 28 in one unit and pick up ready for money and everything so you can see. Now, because change is much more. Interact with each other over much longer lecture. And this is what gives Paula's great distinctive properties as compared to the chains are very big. They can interact with each other over very long distances and they can have multiple interactions with different chains over those. And that's what makes problems so useful is their long range gas. We provide it and we get a solid, but it's usually made of applications. Nathan possible i'll come back to that a little bit later but you probably know things like cling film or it's very stretchy, final, very useful material for things like that as well it can be. The plumber trains can have different types of interactions and refer to these as either umm crystal line or amorphous types of. Snacks next to each other is where there's a strong interaction between the form of change and we get what's known as crystalline semi crystalline region. This is what gives, uh, the former properties like stiffness and strength. We also note that we have these enormous reasons. These are regions don't statistical wealth. They have a random orientation and they don't have very strong regression. These are responsible to get in the form of these flexibility and the ratio between crystalline and enormous regions in the whole material. Ultimately controls the properties on that point too. I can pay that to a small model. Let's say this is sodium chloride, then sodium chloride. We have a crystal and chloride organized in a polycentric cubic. So basically that's each time. In this case only has interaction with the surrounding iron. So for example, this blue iron is only has an interaction with green irons around it. It doesn't have. Can have them directly from training all the way over here. Have a much longer length scale for distance. Why did this run the difference between owners and small modules using this analogy network, it's a bit like a hay Bay around Haydale. If you pull out one straw for that hay, then we're going to maintain to take it. All the straws are into 12. They'll interact with each other. We've removed one of those. It's not going to cause a bell four part and that's because of all those tools. So material is quite part of exactly so much doesn't have a very little and that's because we start taking atoms collapse of it, that's what makes more and they like a brick wall. We start if we take straws out because it's flexible and long range of directions. You can adapt to that. It's actually all this homeless these long range interactions and also elastic and boil at the same time and they can also be heard of things like acid things like falling fiddler so you can draw ponders and find them to make long fighters and he can be. I'm joining to find it many meters long, is obviously colored and has a security feature into it and then cut up into the plastic bank notes. We can also do. We can also. Plastics, that means we can melt them and we can set them. So injection, we have a metal, we inject the polymer and it sits inside the mold. So for example, that could be a chair, it could be things like no bubbles or bubbles that you get. OK so move on we both properties so for example, if you've got a it's a plastic and flex it, then that's a problem you can actually serve. And these properties material are dependent on how the microscope you mean, is it is it crystalline? Is it semi crystalline? So how does change organizing? Or is it a combination of those in many cases or a lot of you actually combination. So the problem mythology, the way those chains. Good noise is in turn dependent on the chemical position. We're going to look at the chemical constitution a bit more details to help us understand how the common changes. So this is a really nice example. I know it's not sympathetic problem. I really love this example. It's really all familiar with Spicer and I've heard that on a wait for weight basis Spider-Man stronger from steel. I think that's what you think here is that spiders don't just make one type of silk every spider has the ability to make different generate a flexible so we're going to be exposed to the rain and wind, so it needs to be able to be flexible so it doesn't break. On the other hand, if the spine is going to trap some prey, it needs to wrap up that tray tightly so the spine has the ability to change the properties. So how does it do that? It doesn't changing the chemical composition of the proteins from which the symbols make. So if you go. To the liquid up middle 2017 basically made protein. It's a it's an amino acid placed protein and it's a very specific sequence of amino acids. So by changing the sequence of amino acids, the spider is able to change the way in which the common chains organized. So for instance, this is at a no scale. This is the form of chains and they form these crystal libraries. Now the Toyota can engineer approaching degree law and engineer to have a certain number of crystalline regions and a certain number of shown here. So the protein could fall. So we have these crystalline regions toughness to the soup and we have regions that can be flexibility. So by changing the sequence despite it can change the ratio of the mothers to crystal regions and therefore can change the properties of the generates when it does this for different applications. The draglines for dragon difference between 2 comments is that in a propylene structure, they pull the backbone and we have these pending. So this is the structure extended structure. So the properties of polypropylene can be changed based on how those are organized along. And you can see that the structure has been drawn three times. Here we should look at. Is how can it was organised respectfully job. So if you look at this first structure, you can see that we have an formal chain and all of the metal groups are coming out of the corner chain in the same direction. So for instance, we have this wedge bond, the side wedge bond that in case of those. So if we have metal groups aligned or on the same side of the structure, we refer to that as isotactic. We can also have arrangements with those default groups to alternate. So we've got a backbone and we have. Back into the screen so much don't have to watch it so you can see they're also making different sides we also have a third arrangement and that's known as hate attic. In a tactic, the arrangement are in a random orientation, so there's no particular order. So how they're organized with respect to each other. So by changing carry i'm going to use to make things like level on top right hand side. So that's it. These are made from my static here. And I can compare that to a tactic point quickly where those aren't organized background and the polar chains can't get close together and the interactions are very weak. And in fact, a tactic is actually a business liquid rather than being a solid. And that's because the interactions between polymer chains are actually. We're not having the organization of those new problems facial penny which is known as the homosteria of pentry or tactic and we'll come back to that in a second so those are for examples where the properties of the performance can be controlled by the national chemical feature. The second second is the second. So this sequence arises when we have more than one might be made from multiple different units and however units are organized as a sequence chemistry with tactic. Just look at that on the previous slide and that's a spatial arrangement for the units. And finally performing architecture, fin but when we just come to the people, OK, so let's look at a couple of examples to exemplify this. So you might have somebody might have these hands in the car so that you can stick your phone to it. All these toys with the sticking feet and then they walk their way down the wall. So that sticky paddle, sticky pants is made for a formal known as polyethylene structure. That formula is shown there 1. OK, let me compare that to a slightly different type of corner and that's known as perspex. It's actually. It's a very hard transparent plastic sometimes, usually replacement. And you see here's a structure of polynomial gone back away. It's extremely similar to structure of polynomial. The only difference is the Nephil group along the. Has a lot more crystalline regions than polyp, so polymer accelerates very soft, is very nervous upon morphology, very morphous and that's because the problem change don't interact very strongly. Please meet on Acrobat has much stronger interactions between the corner chains because of those pendant leaf algorithms and therefore more of the line regions in the following Bristol harder and solid. This is not example where very simple differences in the polynomial, sorry composition can change its properties very drastically. Sequence is how the of course, if you've only got 1 model unit then we can't have a sequence and in this this case we have as known as a corner. Good example of cope on that is polystyrene toe butadiene. Umm and this has this sympathy pretty much replaced latex in the manufacture of things like cartilage. So your car tires are made of this copilot that consists of siren units and butadiene Wikipedia. Now you can organize those two different repeat units in different sequences. So let's say that one of these is repeat unit 8. So we can organise those in different sequences. For instance we could have the A&B repeat units in a random orientation, so shown here we can have an alternating sequence, so one monomer A followed by B followed by A followed by B so on. We have to also want block an A lot of B what an 8 and that's a Tri block performer. In theory, you could have made lots as you want umm, but really have these three main different types of sequence random alternating and then block coordinates. And the the sequence actually has a big effect on properties. And so for example, in a random a random code polymer, the polymer chains might not be able to organize very well and respect each other. Then the. Nature is a great example of controlling or sequence of synthetic chemists. We have never got to this level of control. But if you think about things like proteins, then proteins are made natural polymers, then made amino acids, but those amino acids are arranged in a very specific sequence. Now if you think that is approximately 20 common amino acids, there's also a lot of product. Left corner ones as well. But just taking say 20 chlorine acids, in theory you can organise those 20 amino acids in an infinite possible number of combinations or sequences. Do that you can make proteins that fold into a particular structure that gives the protein its function, for example enzymes and this is what this needs to complexity in life. So nature control the sequence of amino acids that controls the protein folds, forms a larger or structure and that gives function to that particular protein. Stereo chemistry or tactic so we can have free at the top, it's a tactic where all those kind of groups are aligned or off or including the same direction. Senior tactic we have the automation arrangement and then a tactic where we have that random. Effective owners then generally within a mixture of corner chains, then the length of those corner chains are not and we have a average chain, average electoral rate. So let me talk about the best partners and talk about the chain making the weight. We actually refer to it as an average because not all the chains are the same length and that's very different to things like proteins or peptides that have a very specific molecular weight. Let me talk about poems. We refer to the average molecular report. The average molecular weight in the unit known as Dalton's One Dalton is equal to 1g per mole. And finally the Pullman architecture. So this describes how the pulmonary looks. We are examples we've looked at so far have been linear problems. We just have a single long chain like this or single long chain sort of branching coming off that. Obviously if you introduce branches, so we have a corner chain and then the branch coming off that. But now we have a branch architecture. There's those branches will join other branches and we just have one cross-linked massive network that's a cross link power network. And that's just where every change is drawn to every other channel. So an example of where the polar architecture and the molecular weight have a big effect on polymers. So as I mentioned before, polyethylene can have different length chains, but it can also have different degrees approach and it's the ratio between the nickel, right and the amount of branching that actually control properties. So you think of umm blah blah, cling film. Then cling film is where we have quite low molecular weight change and we have lots of branches. Now because we've got lots of branches, it means that the polymer chains can't interact or skip close to each other and we don't have very strong interactions. So we have very few crystalline regions, lots of amorphous regions and that means that. This type of polyethylene is referred to as low density. Polyethylene is very soft and flexible, usually making things like. I can film and respect that We increase the molecular weight and decrease the branching. Then the polyethylene chains will start getting closer. We get stronger interactions, we get more crystal languages. So as we go from low density to medium to high density, then we're increasing the overall metal weight on the chains and we're decreasing the amount of branching. This allows stronger interactions, more crystalline regions and we have a much tougher polyethylene. But if you think like agro furniture and and and Carson, we can also go to ultra high level weight. So this is very high level, pretty much no branching, very strong interactions. These types, polyethylene are very tough. They're used for things like bearings could be an artificial joints, for example. So this clearly is an example where control between the molecular weight and the career branch has a huge effect on how. And the properties those features are controlled, these are the chemical properties that control the polynomial control and we want to looking at how we can change the properties problems. So lots of plastics, particularly those that are firmly processed consist of. Consist of both semi crystalline and amorphous regions and you can see that's demonstrating here in this illustration. So we have some crystalline regions, some amorphous regions. These types of plastics are known as thermal plastics and that's because they can be thermally processed. So in these types of plastics, those crystalline regions are held together through non prevalent directions. That means if we apply enough heat to the polymer then we can break those interactions and all the polymer chains become amorphous. At this point we can process the polymer into a particular shape, for example clinical, and those crystalline regions will reform. So this is a typical process or processing of a thermoplastic. This is a bit like when you start off with a bio chocolate, gently warm it and you melt the chocolate you can import into a mold, let it cool down and it will set in that mold to a particular shape. Therapist it's a bit like a bar extensively, an example of whether using the Farm super sector is obviously for making blister packaging, so packaging for tablets or tablets and you can see that the list of packaging has been made through injection molding, tablets been added and there's a full field on top. So this example where thermoplastic only things like Polygon chloride are used in the Pharmaceutical industry. So that's fantastic, but not all polymers have crystalline regions. Some polymers don't interact very well with each other, and they're polymerthology is almost completely amorphous. So that means that the polymer chains don't have any strong interactions. And you can think of this a bit like a plate of spaghetti. In all the plate spaghetti, the individual spaghetti chains don't form those crystalline reasons. They're just entangled with each other. And if you tilt the plate of spaghetti, then it's just going to slide off or float. And that's the same way that amorphous. Behave like viscous liquids or tacky salts. They're able to fly so really good for common example of amorphous polymer are polysiloxides. A typical structure of polysiloxyn shown top right. And these are very viscous liquids only used in the past have been commonly used in things like Britain. So how do we take a polymer such as a polysiloxane liquid and make it more useful? Obviously for some applications we don't necessarily we want formula and has a particular property make it elastic. So how do we modify? The answer is we need to cross link the form to then cross links between the form change in the network. Then they can't flow under each other and we can go from a liquid to a solid. We can see in illustration here we have our amorphous polymer chains. They're not interacting with each other, they don't flow over each other and the former acts like liquid. So if you start introducing prevent prospects between. James like a little no longer flow past each other. And then we convert the liquid almost such an example of a vaginal contraceptive that's made of polysiloxy. This has been made from cross linking of a liquid polysiloxy. So by forming those cross links, there's the bank cross links between the chains. We generate an infinite polymer network where the chains will tangled here. Another example of this is rubble latex. So latex used to be isolated from the rubber tree and you actually tap the tree and let the latex flow out. It's this sort of oil suspension of latex particles in water that's been processed to form rubber. But initially those latex particles are an amorphous polymer. They don't have ticklish. So what we do is they cross link those polymer chains. So this cross-linked tangle network is the latex. They then introduce these dark slots or these cross links between the projects no longer flow flow over each other. And we've converted the liquid latex into a solid elastic latex. I say elastic because if you if you apply a force so you stretch that network polymer chains with the entangled polymer chains could start to unravel and stretch out. So for example, you can see. Started to untangle and the former material has stretch or increase the length because the form change across me. Once you release that force, chains will snap back to the original size and shape and this is what gives rise to elastic materials. The latex gloves are making this way. Start off with latex. It's cross-linked. Generate this elastic cross-linked network as usually also made of rubber or derived from latex. And once again that's cross-linked rubber where the latex has been cross-linked to generate plastic. So these types of polymers are referred to as a lesson because they are able to deform and the form of distress and then return to their shape. Now, you might be surprised to hear this, but you always carry it last night. In fact, you wouldn't be alive without it. That last night is your skin. So your skin has very different proteins in it, but the main constituent is a lesson. The last thing is a lasting protein. It's able to stretch under forces or deform under force and return to its origination. Under a force, the polymer chains can be formed, but then they return back to their original shape once you remove that. They're related to last numbers, are another type of polymer for hydrogels. So hydrogels have to have a similar structure to Latinos. So they're currently crossing polymer chains rather than being hydrophobic, they're hydrophilic. So what that means is that when you put a hydrogen water, it can absorb and swell, take up that water, but because the network is cross-linked, it won't dissolve. So for example, if we have a cross-linked hydrogen network, we have water, the most common chains can and take on the water and in many cases run through 10s or even thousands of times their original mass by taking on that water. So you can see this example, we have a small amount of dry gel add water that and it's grown immensely compared to the original mess and. Result it's just stretched all the chains had a load of stretch and a load of water coming to all the network. So you know this podcast so example where these are used in Pharmaceutical industry is in this integrates for tablets. So you might heard of this is a cross-linked vinyl and it's incorporated tablets. So once the tablet gets into your stomach starts with water they rapidly that causes. Because probably don't do swell and tablets and since we. OK. Finally, the last type of pollution looked at thermoplastics. So these crystalline and amorphous regions, we look at amorphous formers, but you can also get formers that are pretty much predominantly crystalline in nature. So as you can imagine, because they're almost crystalline, these are very hard and tough materials and in many cases are quite brutal as well. These form because the intellectual forces between the chains are very strong. Chains are very good organizing. There's lots of interaction between those. Check. Good example of this is queuing. Umm, So if you've ever, ever seen body armor run by police or street guards or most of my equipment, umm clothing, then that has Kevlar in it. And what Kevlar is is is this probably a mud structure? And what you'll notice between these individual corner chains are these hydrogen bonds. Now, because the polymer chains will be clear, my chains can organise very neatly next to each other. Then there's lots and lots of these hydrogen bots. That gives the mythology very, very crystalline. And that's why Kevlar is really useful in things like body armor because it's impacted this. Once I pull up more knife hits the corner network, then the force is actually dissipated throughout the network because of those hydrogen bots. So Kevlar is regular. Enforce which makes it a very impact position material. The only problem with Kevlar is because of these crystalline regions is really difficult process. You can't just melt it and then commit again to form a particular. You actually need to dissolve it in very harsh solvents in order to spin find it. So you can see that concentrated sulfuric acid is needed to actually resolve. Break apart from the network so then it can be responding to fighters to make things like body on it. So many is one example of a very crystalline polymer that's very useful, but generally very highly crystalline problems are also very brittle. That means don't deform or they're not pliable. So if you compare polypropylene versus polystyrene and you can see this is a polymer has been stretched like that and the polypropylene then you can see that the polymer rod has stretched but it hasn't broken. So in this case. On the right hand side we have polystyrene and once that's been stretched, you can see that the format is actually broken. So it's and quite a few polymers like this and they're not particularly useful in applications where you need the material to be a little bit flexible. So this is where we need to improve or break apart those crystalline regions to improve, change the ratio of the amorphous and crystalline regions, then we change how brittle or. If you reduce the number of crystalline regions and have more regions and then the material will be more flexible. So to do this, we have what's known as a plasticizer. So plasticizer is a small module that interferes with interactions between the chains in those crystalline regions. So because we reduce down the number of crystalline regions, we have more amorphous regions and the material is more flexible and ductile. Common types of plasticizers are bisphenol a chalates and fatty umm fatty that's decided umm, but Bradley overtime research has actually shown that they're toxic. So in in umm more modern plastics, there's been a ship. A nice example of where plasticizers or different amounts plastic sizes are used to change properties of plastic are polyline chloride. So Polygon chloride is used both in a unflastic size form. So we have lots of crystalline regions which made rigid and tough. That makes it useful for things like window frames that aren't exposed to environments where they need to flex. If you had a little bit of plasticizer, then we now generate a more impact resistant flexible polygonal chloride. This is usually things like water pipes. They might be exposed to forces that would otherwise cause them to break if they were a little bit flexible. If we had a lot of plasticizer, then now we form transparent, very flexible medical treatment. So you can see by having different amounts of sizes we can significantly change properties. And the applications support. OK, we've covered everything. I want to do a bit overtime umm, but please, if you've got questions guys, then feel free to speak up or something in the chat and we can have discussion. If everything makes sense and you've got no questions and obviously feel free to, to move on, leave. But umm, now please have questions and feel free to ask, ask away. OK, good morning everyone. Hopefully you can all hear me. I'm presenting from home today. I do have a dog. Sometimes he gets excited so if he starts talking I do apologise in advance. Thankfully he's just. So as I left yesterday, I put the chaplain, well, if you've got questions, if you go along, please feel free to chat or you can wait till the end and we can discuss them then. So today we talk about drug polluting implants. And before we get into it, there's a really nice example of one of these drones in plants on this title slide. So you can see the implant here shown in yellow. So it's a tiny little rod shaped implant. This particular one is made. And it's designed to be inserted into offering so it's only going in the eye and release glaucoma medication over. of 6 to 12 months. You can see that it's extremely tiny and one of the great benefits we'll see about geology implants is that they can deliver a sustained therapeutic dose of a particular therapeutic medication over a very long.. We normally might use eye drops eye drops leads to a very high initial dose that take us off very quickly but I saw the therapeutic window for a lot of the time administering eye drop if I don't implant is that you constantly provide a fairly dose of medication continuously and you don't overdose or underdose. OK, so let's explore. To answer these following questions, I think we're gonna come in today's lecture. So we'll look at different types of drug eluting impulse. So you also need to learn what the different types are. You also need to learn about different types of drug. As we go through, we'll look at the relative advantages and disadvantages of different types of local parts. So hopefully by intellectually should be able to answer all of these questions. You're probably familiar with these types of rafts where we have time on the X axis, representation plasma on the Y axis. And as you can see, there's a therapeutic window shown here by the dashed lines. And really when we administer medication, we want to be within that therapeutic window. The reason for that is that if we're higher or if we're delivering more drugs in a plasma required, then we're overdosing. This can lead to side effects and also wastage of the drug, particularly a very expensive drug. If we're below very good we know that we're under those and we lose any pot this is a typical sort of might expect for somebody taking a oral tablet formulation and having repeated doses every day or multiple times a day, whereby initially the concentration rises very quickly outside the window and then decreases into therapy window for dropping out and reducing that medication is quite however, recent years or probably last 23 years there's been developments in terms of making sustained release or time release therapeutics. You could be all tablets that designed to release over a. of maybe several hours and you can see that initial scenario we a bit more time compared to conventional dosing before dropping out. These type of sustained release formulations becoming various different types. So we can have for instance tablets that have a slow dissolving coating. We also have things like emulsions and suspensions. Please sustain release formulations are designed to release the drug over short.s and try and maintain. Natural.s this is person has eaten food or hasn't massive effects on the release and the part of availability depending on the environmental factors. Once again, formulation in this particular case, even if sustained release, you do have to have a piece of administration. So rely on people are patients taking tablets every day or multiple times a day and this can obviously lead to patient compliance issues. No. We would ideally like particularly given a patient umm 1/4 location over a long., say months or a year. Say that we have a a constant concentration inside the package window over a long time.. Type of devices or formulations that give rise to this profile give a zero order range profile. That means they're constantly releasing the same amount of drugs for every time.. Is what we see in a lot of cases for drug emerging implants and This is why drug leasing imparts will be so useful. They can deliver a sustained or control, they can deliver a constant amount of drug inside therapeutic window over a very long. of time depending on how you design the revolution impact. Voices are implants that are more devices are implanted in the body as a language, yes. So this could be subdural, subdural so under the skin could be into Optima, so in the eye and they're designed to release their payload, their drug, their therapeutic over a. of months. Very long release. of medication. So the advantages of these types of Android implants is that they can give you a very fixed and regulated amount of drug over a determined. of time, so. The same. and that can be weeks months not days, but ranging from weeks to months to years. Umm, because they implanted in, uh, they don't, They don't involve, umm, passage through the gut. And they invited something. Then we don't see any significant influential environmental conditions such as whether or not people have eaten or whether they're not, as we do with all formulations. And the other big advantage of alternative parts is that a doctor convinced them and then we don't need to rely on patient response. Look at some different types of control release fusion control, there's also chemistry control, solar control, activated and modulated. First of all, let's have a look at the fusion control systems. So he's broken down into what language, reservoir systems and matrix systems. The point here that matrix systems are not available or non regular. So these are made from materials that don't degrade. They're not biodegradable in the human body. Have a implant that has a body and it has a cavity, a hole in the middle with as long as loaded. See that we have this blue sort of shell. That's the part of the implant that is the solid part. And then we have the drug in the center of the vacuum part. That could just be the solid drug. It could be a drug. Fortunately, it's always look within 400 months. So when that impact is implanted into the body, then water starts to diffuse through the outer layer of the implant. I should mention here that pretty much exclusively the implants are made from corners and these polymers are not degraded. So they're not biodegradable, they're not breakdown the body, but they are parable to water and drugs. That means that water can diffuse across that. And we get that controlled release sort of profile now also as a concentration of drug in the environment decreases then we see a gradual decrease in the mouth. So we don't get a true 0 or release and you sort of tend to see the ghost at the time. So decrease, but you can engineer it is maintained within that therapeutic unit now ultimately when all the drug. Don't be released they're gonna see is that because they have that: cavity where drug is then they are prone to potential fracture? I suppose the last potentially be mechanically deformed were broken that can lead to a fracture in that as a form of hunting. So if this happens, you can imagine that we generate a small hole fracture in that coating and the drug convey rapidly be released through that fracture. And it can lead to a scenario where we have a burst release of the drug into the surrounding environment and can lead to very high overdosing, which obviously potentially cause side effects and depending on drugs. That will be fatal. So this is a inherent design for these types of devices are these types of diffusion control metabolic systems. And that's why it's very important to maintain integrity in that outer corner layer so you don't get fractured like that. Those that sort of issue can be avoided by having a matrix system. It's now rather than having a party in the middle of the environment, we have a solid implant. So solid column matrix and the drug is dispersed in that matrix. Here we have our blue polymer implant matrix illustration. Overtime water is able to permate into the implant is all the drugs belonging to diffuse out in the matrix system. Once again, overtime the concentration in the concentration of the environment decreases. So we do see a gradual decrease in the therapeutic amount of time, but you can maintain that relatively long.s. Once again, it's not shown on here. Released from the diffuse out from the impact. So these are two types of diffusion control systems and matrix own differences within the reservoir in both cases we're using a non durable problem. They could be easily injected as well. You'll see many parts are based on these one sort of structural forms. In the case of the diffusion control systems that we're talking about, the reservoir and matrix diffusion control systems, then a disadvantage is that the polymer is non degraded. So that means that once the advantage is missing all of its content, all the blood, then we need to surgically remove the impact. So that's not necessarily that difficult, but it does ******* what they have to have the environment move. Let's finish the reason. As I mentioned before, in this time system holder is; water and that's what. Should I form the matrix now during yesterday's lecture, then some of these honors might be familiar. The commonly used farmers for future control implants are things like polyethylene COBRA. This is a very common formula used for drug implants and also polynomial back electric to a certain extent. So reformers have different probability characteristics and that means that to an extent you can select a different polymer to give you a different release profile so these columns might be more or less available to work and therefore that allows so you might go faster release of the this is something like more homophobic. So the selection of the polymer for the future control system you want to make is is very important, allows you to control that drug release to a certain extent. Initial burst in the reservoir system. So the initial burst in the reservoir system only occurs when we get a fracture or some sort of defect in that anthropolor shell. If obviously if there is a hole that generates the void of rushing through that hole, there's all the drug and then obviously rush back out through that hole. So it's no longer diffusing across that polymer shell and it's simply going out through the whole fracture between generating that whole. Really, really haven't possibly familiar example of a diffusional system is the this is a implant that's releases a hormone concept and image of the uniform here I'm also here. So this implants actually quite large, probably about two to three centimeters in length, maybe a few millimeters in diameter. But the input on implant is a diffusional metric system that's a solid polymer. It's actually polyethylene photon accepting and the drug that they released is first to be that follow metrics. So it's implanted using one of these devices. So just basically a needle and the implant sits inside this cartridge. The needle's inserted on the skin and then the plunger is pressed to as the knee was retracted to put the implant in place. Under the arm three times the implants provide up to three years of birth control concept of medication, so they provide a very long. and. Doesn't it require them take a tablet or kill every day? Umm, they can get a reminder when it's taken out and go back to the doctor and potentially get another advance a new implant. But obviously we need to remove the old one because it's not by radical so it needs to be surgically removed once it's finished. So these are the advantages and disadvantages for so it can be implemented for rejection and this is pretty common to all, especially if they're not shapes, they're three of them. First objection in the case of these matrix systems or the reservoir systems, and they're relatively easy to fabricate. You basically just now with the drug and you extrude that into a fiber. They provide a controllable release profile and there's also quite a few of these different types of diffusion control systems already on the market. There's a lot of presidents for the safety and efficacy of these parts and disadvantages and this is probably the biggest 1 is that they're not degrading to enable non binary. That means they need to be searched to be removed once they finish the meeting their jobs. In the case of the reservoir system, then we do have that slight risk of fracture to the antic on the shelf that can lead to a first release and overdosing for the medication. Generally as well, these efficient control systems have relatively large trouble. That's not a major issue if you have a very close drug that you don't need to load very small amount anywhere. But if you have a drug that you need to deliver a larger amount, then this can be an issue because obviously if it's not, then you need to have a Monet in your implant. Therefore you'd be a very big implant. The reason why drug loading is that you can get inventory low is because if you have too much work there, it starts. To affect the integrity of the polar matrix. Probably less than 10% more like 5 just released a therapeutic of the drug based on chemical process that could be metrics, for example. So you can look at two of the types, uh, make. So these are where the whole matrix is either bio erodible or biodegradable. Umm, in these cases the drug appears long can I incorporate into environment. So this is these metric systems or chemical controlled metric systems are similar to the diffuse controlled metric systems in terms of how the industry looks. They're very different from the mechanism by which they. Second type of kind of control that I did want are the drug department fungus and these are where we have to have the drug directly conjugated to polymatrix and the reason the drug goes through a hydrolysis or enzymatic degradation process. So first of all the chemically controlled matrix system. So as you can see it looks a little bit similar to the non biodegradable diffusion control like polymer matrix shown in green. We have drug shown black for the dots dispersed within that polar matrix. That's that polymer is, but it is to a certain extent soluble in an anchorage environment. It might have very low solution in many cases that's what you want. Is that controlled? Then we have a bioavoidable system. So this is where the parliament doesn't degrade, but it's slowly resolved. And that's showing this second image here. So you can see the polymer at the surface of the environment is starting to become migrated. Once it reaches a certain hydration, then it comes stabilized in the surrounding environment. Now obviously during that process, the drug is dispersed within that folder, is released into the surrounding environment. By the time we get more and more dissolution of the polymer matrix and then more and more block release. There is any sort of system, umm, you can see that the drug isn't so much as diffusing out of the common implant, but the drug is released when pulmonary is dissolved. So this means that we don't see such a big drop off in the drug concentration overtime and what really effects the actual dosing is the surface area that's being dissolved away. But generally we see a relatively consistent unfairly those being delivered over the lifetime of the impact. Now they buy the gradual system is very similar to this, but rather than deployment is only, it's actually degrading. So the polymer is being hydrolyzed or enzymatically broken down into smaller soluble fragments. As they get broken down, graded and dissolved, then that results in release of the drug that was within that part of the. As overtime more and more we think they should curse and we get more and more drugs. So both these systems are quite similar, one's based on a dissolution or bio corrosion process, one is based on a biodegradation process and we get because that progress occurs at the service of the environment, we get the drug from the surface randomly deep interior of the implant. Obviously, depending on the polymer you select, whether or not it is also degrade or degrades and the rate at which those processes occur, you can control the rate for the least drop. So if you want your implant to slowly release the therapeutic. of year. Select that has very low water solubility but it does have a small amount so that means you can choose the drug so maybe see these types of impulse. Well this is an example where a bio rate will make the system have been used to actually provide a coating on a stent. So you're probably familiar with metrosense like this inserted into arteries to when you have narrowing of the artery. Through the door of the blacks. Common problem with these types of no sense is that once they are inserted in place then we tend to get a process that cause the causes narrowing of that blood vessel again. So restonosis occurs, tissue from the surrounding artery starts to grow inwards and that can be around the ends of the stent or in the middle, but the ultimate effect of that is it continues to cause narrowing of the artery. My recent years people started to use metals to actually have a **** film total service so that's them and that folder film is a bi degrading matrix system. So within that Bond film there's a drug that inhibits the rest of nieces process. So once these stent is still inserted that body rate will fill on the film from the joint side starts degrade very slowly that releases the drug into the surrounding tissue and the drug impedance the resolution process so it. And there's a video here that you can watch in your own time. There's a link to it there that shows one of these commercial products that are available that format. So the second fight the chemicals drug releasing impact or do you want to call the consequence? In this sort of implant, we're actually now conjugating drug for covalent linkage. So let me have a rough shake plant. These rush implants for drug conjugates are made from a foreign map that has the drug already important. BBC here. It's happening to Brooklyn so I had two different types of one there is dependent 1 known as the engine. So as the name suggests that describes the orientation of the drug with respect to the following. Now here yesterday's lecture you know went through some basic dementia or palmers and we have the polymer backbone. Anything that dangles off the polymer backbone is known as being pendant to that polymer backbone. So in this particular. Those drugs are pendant to the form of backlog obviously showing blue here, drugs in black, and they're linked to the corner by a hydrolyzable link. So that linkage there showing orange between the corner and the drug is a cardinalizable link. It's a bond, but it can be either hydrolyzed or broken down by enzymes to release. That means that when that process occurs, then we get the release of the drug from and the. At least you know Freeport, that means it's released as the original drug from therapeutic drug. This is obviously distinctly different to the in chamber. So here now you can see that the drug is actually in line or in the polymer chain. So polymer chain actually has the drug incorporated along the polymer. The linkage between the blue segments and the drug are hydrolytable. So that means that we can get cleavage on either side of the drug to release the drug. However, because of that particular mechanism, then you could envision a situation where we don't get complete cleavage with all hydrogen bonds. So what that means is that when a hydrolysis event occurs, it may not always release a free drug. It might in some cases where hydrolysis appears on both sides of the drug, but. In some places, it may, uh, release drug on fragment. You can see that we have drug connected to some polymer still. And this can be a problem because obviously we're not always releasing the free drug that has the heritage effect. Some of these pollen fragments might have no therapeutic effect or because they have that pollen fragment there, they might actually be toxic. So this is a inherent problem with in Chamber of conjugates. We're not always releasing the free drug, which is distinctly different to a pendant. So we could say that for a pendant drug, polyconjugate, then we get efficient drug release. Every hydrolysis event results in the release of a free drug model. In these types of drug conjugates then we can typically get pretty high loadings. So 28% of drug that's significantly higher than things like. You can choose different corner backgrounds then that allows you to have good control over the material to how you process the drug conjugate pull up into different forms. So for example how you manufacture the polar into a fiber. Now compare that to and you can see that we get extremely high loading. So you can get up to 50%, even more in some cases of drug along with common backlog. However, because of that very high drug loading that means the properties of the polymer are heavily affected by drop that can lead to issues and more control during the manufacturing process. The version of that corner into an implant. The other issue that I mentioned previously is that drug release relies on hydrolysis on hindsight in the drug market. If that doesn't occur, then we potentially release drug on the fragments. These can be inactive or even potentially possible. There's beautiful ways that we can make uh, drop on the conjugates. So the first one we look at is a pendant drop on the conjugate, and you can see that we can start off with a intact polymer. And so this is our long polymer chain. It has pendant linkages attached. We have reactive functionalities on the end of these. We can then conjugate the drug, so we can currently attach it to the end of these linkages and we end up with our pendant. This isn't necessarily the best way of manufacturing, and that's because we tend to get stearic endurance around these linkages, particularly when drugs are quite bulky. So that means you don't always functionalize every potential linkage from the drug and we end up with a scenario where we get lower drug luggage simply because we don't we haven't functional conjugated 100% of the drugs to 100%. Probably a better way of making UMM complicates is actually start off with a clearisable monomer that has the drug attached. So you have your monitor, every monomer has one drug attached. When you pliarise that monomer and you end up with a drop form comes up where you know that every linkage or every repeat unit along the backbone has a drug attached. So you can see that we get 100% of the drug incorporated into the pond chain if you follow this video here. This is probably Activa. This shows the example of their process for making drug. Now the in chains of conf. A Mona or a short honor and you react that with a drug. Obviously the drug here acts as another monomer. So it's like a funeralization and the drug has to have multiple functional groups and also attached or incorporated into the former chain from on both sides to drop. Some drug needs to have multiple ways that we can prevent incorporated into polymer. It only has one reactive functionality then we can't make a continuous polynomial, it has to have. True, in order for it to be incorporated, people change. I'll show you an example of what I mean in a second. So this is an example of a pendant drug called conjugate. Let's take it from the literature and what they've done is they started off with a polyglutamic acid. So this is you can see that we've got a Polytechnic backbone and we have these pendant. Make a call on the 1st and then they're attaching the drugs and the drug they got here is and you can see that they've got a short spacer group and they've reacted that counseling actually with the hydroxyl group to conjugate those together and form an estimate. So you can see here we have that linkage between the backbone and the drop. So because we have an Ester, it's hydrolyzable. It can be broken down by enzymes like lipases. So in the body this linkage would be hydrolyzed and. Get a list of the drug. We also see hydrolysis of this estate here as well. So potentially we can have two points of hydrosis and release of the drug. That's kind of the way this has been manufactured. So they make upon the first they're attached to drug. They don't get 100% fertilization for dependent groups. They have some three that don't have congregate drug. And this is the release profile taken from the same way. You can see it's not perfectly 0 order, but it's still pretty good. Over the 1st 60 days it's ready to be linear and then we tend to get slight decrease. Like samples, but they've got mixed over nearly 180 days. So this is part of this part of the design. Umm, provide quite a long, sustained release of the drop. Flexing and you can see that this is the problem yeah umm. This particular model has a secondary alien here that calculate acid reactive functionalities on other side. This allows it allows us to incorporate it into a polymer that's one moment the drug is 1 / 2 reactive functionalities. We also have a second one over here. The structure isn't that important, but you can see that this one has functionalities on both ends as well. So it can react with two functionalities from the. So we end up with in chain drug for the contractor where we've got umm, compromisation of both of these together. So we have the spacer group and then we have a drug space group, drug space for drug and so on and so on. So in the case of Congress gets important that the drug module has multiple reactive functionalities for which we conjugate it into public chain. So once again, the advantages for these systems that implanted for injection, particularly if they're for instance, Ross, because these chemical control release systems are either by a rotable or biodegradable, that means they. We can get hydro loadings generally between 20 and 50% and if you pick your polymer and your conjugation chemistry correctly then you can have pretty much 0 release profiles for these systems. The disadvantages are that compared to the future control systems, the manufacturing process here is a little bit more complicated. Particularly conjugate swing do that chemistry in order to attach the drug to the plumber. When we start to get a very high drop loadings, then the properties for the polymer are significantly affected by the drug. This can have issues in the manufacturing process. Phone control systems. OK, so 2 phone control systems, 1 is the swelling polymer systems. These are based on Hodge gels. So if you were yesterday lecture you'll know what hydrogel is. And the second one is osmotic devices. So I find gel is a cross-linked polymer. It's a continuous network upon the chains that come out is attached together. Now the polymer itself can take on water to absorb water, but because it's cross-linked it doesn't dissolve. This is an example of one of these systems. So this is swaying control system. We have the drug dispersed within the hydrogen matrix. That high jump matrix overtime can take on water that swells the matrix creates pause that are big enough with drugs the future. So you can see overtime that whole matrix is swelling up and getting bigger. That's allowing the drug to be released. So for these particular sorts of systems, the hydro is also designed to degrade, but it's designed to degrade along the time scope. So what we mean by that is that the impact is designed to initially release the drug through the swelling process and then once the drug's been released, the highest gel starts to degrade and breakdown. OK, automotive devices. So these are a little bit more complicated compared to the previous ones you look at. This is a typical schematic of a osmotic drug. So what you can see here is that we have a Azure semi permeable membrane, so basically semi parameter water and it's non compressible. So what that means is it won't change shape, it will allow water to diffuse in, but it will keep its rigid structure. Within that you have this blue region that is a solution that has a very high salt concentration. Then we have a internal membrane which is water inferno. So this membrane won't allow water across it, but it is flexible, so that means it can be squeezed. And then we have the reservoir with the drug in it. And finally, we have a tiny, tiny little laser build. So what we're going to see is through the process of osmotic pressure build up. You're going to get depression of that internal membrane and squeezes the drug out through that laser dual hole. A quick recap, I might remember this from first year chemistry. So osmotic pressure which makes when we have resources. So imagine we've got this YouTube that we've got 2 solutions that are separated by semi panel membrane. Larger ions can't travel across its membrane, only water control across membrane. On one side to the blue side we have a dilute a few solution could just be water. On the right hand side we have that red solution that's a concentrated salt solution, so it could be very high inside. So initially the water will travel across this several membrane to try and loop down the highly concentrated site. So the water molecules are moving in One Direction trying to loop down that salt concentration and reach a state of equilibrium between the two solutions. Obviously because wars are moving across in One Direction, that causes the volume on that high concentration, high salt concentration side to increase until we reach an equilibrium point. And that's as long as the osmotic pressure difference. So effectively we're generating a pressure on the right hand side and the osmotic devices uses pressure differential to actually drive out and release the drug. I think that was what would be nice and this schematic here shows how it operates. So initially we once it's implanted then water is able to move across the; as a membrane. Highly concentrated. Something about systems like to reach a state of equilibrium. In order to do that then the one needs to move from low salt concentrations to high salt concentrations. Now because this anti membrane isn't always rigid, that means that when the water moves across it increases the volume inside and that causes the internal membrane which is flexible to be squashed or squeezed. That reduces the volume inside that membrane and therefore. Obviously it's time to buy. More water is taken through that as a membrane increases the volume inside causes more squeezing of that into a membrane and continued drugs release. Automatic devices or implants, I think there's some in particular trials for human use, but predominantly they use for animal studies. And it's because it's because it can be difficult to administer medications to animal on a daily basis, particularly if it's oral and it tastes foul and they might not always take it. And it's just easier to implant advice, let that little drug over the course of the study and don't have to worry about trying to give administration back to. Would that be only for injection? So for these types of osmotic devices then we can control the release of drug by changing things like the porosity of the anti member. The process of the anti membrane is larger. That means the water diffusing quicker and therefore get quicker is less terrible. Then we get a slower ingress of water slower. I need some quick notes on externally activated and modulated drug delivery systems. 3 Throttle systems provide what are known as on demand limits, so they're not like the previously looked at, but we get a constant control release of drug over a.. The user to actually only release the drug when you're quiet. Like I can't believe I have chronic pain and that manifests itself from time to time. Initial devices can be activated in those scenarios and release that medication when it's required. So in order to do that, these types of externally controlled implants need to either respond to electronic stimuli or some sort of external stimuli like ultrasound, light, heat, or magnetic field. There's many examples of these types of vices in the yard phase and probably a few clinical phases. Well now, but one that has already or is already in use is the backward bend pump. This is the device impact the device that's designed to deliver a lot of them and that's the treatment of. So you can see here, this is the picture of the device and this is the this round part is the part that's implanted into the abdomen and then the wire. Here is fed through into these umm, spinal cord. So this is after the into the spinal cord to where it needs to deliver the umm drug. So and this this blue back here that's the externally external data device that's used to control the input. So the user will actually have that externally and then when they need a medication, they can use that to send a signal to the implant that would trigger. They umm, the release of a defined dose of medication. So you can see here. This is the reason why it's sort of implanted in person. And obviously you need to be taking impact anytime if it runs out. So you can actually refill the device with more drugs just through a syringe external. So you can see it's got your hole here that allows you to refill it with drugs. So you don't need to keep removing that implant to refill it with drug or replacement. So I can stay in place, umm, continuously. Good morning. On these little design considerations that we need to take into account when we're developing a drug delegation implants and pretty much in all cases the type of design of drug eligibility implant is specifically they might want to deliver a particular therapeutic, you might want to deliver it for a particular. of time you might want to deliver. There we go. These are also things that you need to consider when you design your implant. Umm, also things like do we need to retrieve implant? Do you want to send it to remove it or do you want to be great? So these are also designed considerations and every drill engine implant is different than is designed for a specific application.ancial structure. Simply the structure of the morning units that's made-up. Remember that it's all the monomers we can write as long as you get the polymer.
Study Notes on Polymers and Drug-Eluting Implants
Polymers Overview
Definition: Polymers are large molecules formed by joining repeating units (monomers). Examples include plastics.
Types: 1) Synthetic Polymers - derived from fossil fuels; 2) Natural Polymers - derived from living organisms (e.g., proteins, DNA).
Structure: Consist of a backbone (chain) and can have pendant groups, affecting properties.
Classification: 1) Crystalline: ordered arrangements, strong interactions; 2) Amorphous: random arrangements, flexible.
Properties: Determined by molecular weight, structure, and interactions.
Drug-Eluting Implants
Definition: Implants designed to release medication over time, maintaining therapeutic concentrations without patient compliance issues (e.g., eye implants).
Types:
Diffusion-Controlled Systems:
Reservoir Systems: Contain drug in a cavity; water diffusion controls release.
Matrix Systems: Drug dispersed in a solid polymer matrix; drug release occurs through diffusion as matrix swells or degrades.
Biodegradable Systems: Polymers that dissolve over time, releasing the drug gradually.
Chemically Controlled Systems: Drug directly linked to polymer chains, releasing through hydrolysis.
Osmotic Devices: Use osmotic pressure to release drug through a small aperture.
Key Considerations for Implants
Design Factors: Therapeutic target, duration of release, polymer selection, and the need for surgical retrieval after use.
Advantages: Controlled release, avoids patient compliance issues, reduces peaks and troughs in drug plasma levels.
Disadvantages: Non-biodegradable systems require surgical removal.
Study Notes on Polymers and Drug-Eluting Implants
Polymers Overview
Definition: Large molecules formed by joining repeating units (monomers); often referred to as plastics.
Types: 1) Synthetic (from fossil fuels); 2) Natural (from living organisms, e.g., proteins, DNA).
Structure: Comprise a backbone with potential pendant groups, influencing their properties.
Classification: 1) Crystalline: Ordered, strong interactions; 2) Amorphous: Random, flexible arrangements.
Properties: Influenced by molecular weight, structure, and inter-chain interactions.
Drug-Eluting Implants
Definition: Implants that release medication over time to maintain therapeutic drug levels, minimizing reliance on patient compliance (e.g., ocular implants).
Types:
Diffusion-Controlled Systems:
Reservoir Systems: Drug in a cavity with controlled water diffusion.
Matrix Systems: Drug dispersed in a solid polymer matrix, releasing through swelling/degradation.
Biodegradable Systems: Polymers dissolve over time, releasing drugs gradually.
Chemically Controlled Systems: Drug linked to polymer chains, releasing via hydrolysis.
Osmotic Devices: Use osmotic pressure to release drugs through a small aperture.
Key Considerations for Implants
Design Factors: Target therapy, release duration, polymer choice, and need for surgical retrieval.
Advantages: Controlled drug release, reduced peaks/troughs in plasma levels, bypasses patient compliance issues.
Disadvantages: Non-biodegradable systems require surgical removal.