Enhancing Peptide Bioavailability with Cyclodextrin Encapsulation

TL;DR

This discussion delves into the critical role of advanced powder processing techniques, particularly dynamic atomization and cyclodextrin encapsulation, in overcoming solubility and stability challenges for peptides. The conversation highlights how encasing molecules within cyclodextrin cavities, or capping them with cyclodextrin branches, dramatically improves solubility and protects peptides during transit through the digestive tract or bloodstream. This approach directly addresses common inefficiencies in peptide formulations, such as residual moisture leading to degradation, by producing high-quality, bioavailable products. The speakers emphasize that while the industry faces high raw material costs and increasing demand for pure peptides, strategic interventions in the value chain, like those offered through specialized contract powder processing, can significantly enhance product quality and consumer value. The discussion also touches upon the careful selection of partners and the application of these techniques to emerging areas like gut health formulations, showcasing the precision and impact of particle engineering in creating superior end products.

Cyclodextrin Encapsulation for Enhanced Peptide Delivery

Hendrik: Within all of what you just said, obviously, there’s a there’s a lot of different pullouts. I thought one interesting aspect that I wanna kinda make a clarifying question on because I think it’ll be really helpful to people watching. The inclusion of cyclodextrin could obviously create higher shelf life, higher saliability, higher bioavailability within the ways that you guys are utilizing them in the manufacturing process here, specifically with peptides. And so a peptide that has a cyclodextrin inclusion could significantly improve its actual usage to the consumer. Does that exist on the market yet? Or is that something that is only really able to be done through the specific manufacturing that you guys are kinda frontiering currently?

William: Julie, I’ll let you take this one.

Overcoming Formulation Challenges in Peptide Manufacturing

Ulli: Alright. When you include a molecule in a cyclodextrin cavity, there’s a couple of factors that are very important, particularly when we talk about peptides. Peptides come in all shapes and sizes., I’m just gonna throw out a couple of technical terms here. A peptide can probably be anywhere from in 60 Dalton more weight to a 130,000. Now that is a very wide span. A glutathione molecule is probably around 260, and then a clotho peptide molecule is a 130,000 bauldtons. You can already see that there is no single answer. What I can tell you is that any cyclodextrin inclusion, be it the approach that we usually deploy for our nutraceuticals where an entire molecule is encased in a cyclodextric cavity or an approach that is more similar to what the pharmaceutical industry has been doing where large molecules are capped on their branches with several, sometimes even different sized cyclodextrin molecules dramatically enhances the solubility, protects the peptides on their way to their destination, and then really in combination with our sodium cap rate has the ability to really freely and smoothly enter through the digestive tract if consumed in oral form or through the blood and organ barrier if used as a reconstituted injectable.

Ulli: And so it is the when you look at bioavailability on its own, regardless of absorption, timing, location, just look at the variable bioavailability. Cyclodextrin inclusion has been proven to multiply molecules’ natural bioavailability to the human body by about factor four or five. Then that’s already pretty dramatic, especially when you have something like a peptide that might only have a bioavailability of 10 or 15%. Now you think about what happens, you multiply that by four or five, you all of a sudden have something quite enormous. And then, of course, in the chain of our technology, now you have the bioavailability created, but now you need to make sure that you have the timing correct where it, deploys this bioavailability and the absorption to make sure that it can get to the exact location where it is aimed at.

Ulli: And so I think the nutshell answer to your question is we are not aware of anyone else who’s doing it with psychodextrin inclusion. Yes. Psychodextrin inclusion is a tremendous unlock of bioavailability, but it has to be paired with the tool kit that we have, and that is a large part of our patent suite to really get to peptides to an unprecedented efficacy.

Hendrik: Wow. That’s exciting, honestly. We’ll move on to the next question here, which is what are spray dried dispersions and why are pharma companies increasingly using them to improve bioavailability?

William: It’s spray drying dispersion is a is an approach to spray drying where the maker is trying to avoid crystallization and improve solubility. And so they’re dissolving material in a solvent, and then they’re they’re flash drying it, and there’s a polymer involved. And so when they flash dry it, they’re dissolving the material and evaporating the solvent, and the core material is left in a polymer, which really, I think, what people need to understand are the two key drawbacks. One, it doesn’t necessarily hold. Things can revert into crystalline form, which is counterproductive. That’s what you’re trying to avoid. Sometimes it works. Sometimes it it slides back into the undesirable crystalline form. The other things, though, are that, one, you’ve got a solvent involved and a polymer involved, and that’s not necessarily what you want.

William: A lot of people don’t really want or need polymers in their material, and yet they end up with one. More importantly, the spray drying itself is usually part of the problem., we’ve talked about this at length, so I don’t wanna spend a lot of time on it, but the spray drying itself is an inexact science.

It’s certainly imperfect compared to the dynamic atomization alternative. And when you compound its inefficiencies such as the residual water, the residual moisture content, and water activity that can lead to mold and APC and so on over time, having these other drawbacks to the dispersions, it’s it just adds to, some of the challenges that you have to deal with. Now it can be very cheap, and that’s why people pursue it., there’s there’s a reason why people do things.

William: Clearly, it’s a decision that, part of the market makes and will continue to make for reasons. If they’re looking purely at economics, short term, don’t care about the drawbacks, not arguing with that. But it’s important for people to understand why those decisions are made despite the drawbacks. It’s usually purely economics and a lack of concern about, the purity or the efficacy of the final product. It’s not the approach that’s taken for a very high end, very sophisticated product. And so it’s it’s just on a spectrum at a very different part of the spectrum.

Hendrik: That makes a lot of sense.

Hendrik: If the whole description, I think, of the beginning context to the question, I think, helped quite a bit with understanding of the economics behind it and everything. And it’s not surprising. It seems like as this as this industry grows, it doesn’t shock me that there are certain companies that are gonna decide to take the lower end pathway to make a cheaper product while some of the people like seems like what you guys are doing are making a much higher quality, much more pure and bioavailable product. That’s an interesting comment. And I do think that to some extent, that gets you even to your next question, how dynamic atomization benefits sensitive biological materials. One of the things that I wanna get us back to where the economics become extremely important is what Will was talking about earlier in terms of the raw material pricing.

Hendrik: There are peptides that cost $70,000 a gram a so when you look at that, what you really if you are a company who’s buying peptides like that, and maybe if you buy a kilogram, the price goes to $50,000 a gram. There are a few things you cannot afford. You cannot afford to lose really any in the processing, and you cannot afford to lose any to forces that you find in spray drying like moisture activity or mechanical shear. Right? So we talked about how fragile and sensitive these molecules can be. And in spray drying, oftentimes, the material is pushed through the process with an incredible amount of pressure, which on the molecular level causes the molecules to rub against them and bounce off of each other.

Hendrik: And then they’re in the in the heat for maybe twenty seconds, and they bounce off of each other. And in the end, they no longer look like this. They kinda start looking like that because it’s it’s physical mechanical forces with which they bump against each other. And that’s why, one of the aspects of dynamic atomization is that it’s a very I don’t wanna say gentle because it doesn’t feel like there is anything gentle about, heating a substance to over a thousand Fahrenheit for even if it’s for less than zero point four seconds. But it is a slow it’s a low pressure process, which is very beneficial. And that’s why I think, our companies are uniquely positioned to work with those specifically challenging materials.

Hendrik: We were out in the manufacturing facility yesterday and had a whole group of absolutely lovely, highly intelligent, very influential industry participants with us. And, one of the things that we were talking about is that in many instances, we are being approached to provide the solution to a problem that doesn’t seem to have a solution.

And so I think that’s goes into that direction, why is dynamic atomization particularly suited? And the answer is yes because it is especially well designed and engineered for particle engineering fragile materials.

William: That’s what you said makes all of that make sense, but that is, I think, even just the very beginning of that to help people understand just how expensive some of these peptides are and how pure and precious they need to be treated. It’s crazy. It’s crazy. Yeah. No. That’s that’s really interesting. People don’t really understand., they understand, that peptides at the final phase, point of failure, they’re quite expensive. But they’re, in many cases, only buying micrograms per dose. And, of course, at the level we’re, participating in the value chain, which is at the beginning of the value chain, working with manufacturers to make their products in bulk in mass better before they flow through the value chain.

William: We’re dealing with, very large volumes of kilograms, and then they’re being sold bless you. Being sold for hundreds of thousands of dollars per kilogram, that’s the friends, family, and hostage price. Because right now, that’s the stage the market is in. There are very few hot ultra high quality producers. There is an Asian supply component. There’s a Middle East supply component, and there’s a very, very nascent US supply component. But the value and the supply chains are still taking shape and it’s extremely important that anyone who’s participating in this market have the materials rigorously tested to make sure they’re extremely high quality. And in order to get the best high quality product, it’s extraordinarily expensive and will be for a long time.

William: For now, until more supply is built up to meet the exploding demand, there will continue to be excessively high prices for pure product at the beginning of the value chain that will continue to flow through, and we’ll keep these products at a very high price even as the FDA begins to route particular peptides into the compound pharmacy channel because demand for them seems to continue to grow as fast or faster than they can be produced at the origin of this of the supply chain.

Hendrik: And that’s really cool to hear as more of an outsider from the industry because, if a supplier is paying $70,000 per gram of some of these really, really high value peptides and they’re going through the processing of that, they have to charge a certain price to the consumer for the end product of it. Whether or not it’s been processed in a way that’s very bioavailable or not. And so I think what’s cool about what you guys are doing is you guys are adding a very specific connection within that value chain process where a company has to charge a certain price for an end goal product anyways, but the quality that the actual consumer is going to get out of that is a big factor.

Hendrik: And you guys are adding such a big value aspect within that I think not only is great for the consumer and, different people who are on a on a more wholesale level gonna be buying the product, but to the end consumer who’s gonna be consuming this or, putting this in their body. And I think that’s that’s a really amazing thing that seems like your company is doing.

The Value Chain of High-Quality Peptide Products

William: Yeah. That’s that’s what we’re trying to do is we’re trying to take phenomenal products that do amazing things for people and make them even more impactful and high quality, for them, for the value chain. What we see is that these products do have an impact. That’s one of the main reasons people are seeking them out in mass, and it’s growing so quickly. And what we’re able to do is apply our technology layer to that so that when people see the Tesseract name associated with the products that we’ve that we’ve influenced with our technology, they’ll know that they’re getting the absolute best, most impactful, most bioavailable, and well absorbed version of those products.

William: And that’s why we’re very selective about the partners with whom we work, the original manufacturers, and the partners with whom we work downstream who take our proprietary powders, our proprietary ingredients, where we’ve reacted these peptides and then incorporate them into their own products regardless of what that product is, whether it’s a powder filled capsule or it’s a gummy or it’s another product for the value chain.

Hendrik: That’s really cool.

I do have another question that I think is very pertinent to we’ve talked so much about how this breaks down on a bigger level and how this works out on a theoretical aspect of different inclusions and different practices and things. But can you walk through a real example, take out the name of the client or anything if you need to, but of a biologic product that you successfully converted to a stable?

William: Yeah. I’ll I’ll I’ll give you two very quickly because I think they’re very telling, and I think they’re very pertinent examples. Choose them, for this particular market segment., there are a lot of them out there. The things that we’re doing, right now for the peptide sector, all of those with partners are under NDA, but I think these things are relevant to that sector. They’re items that are going into these products, but I’ll speak about them, generically.

The first one is a short chain fatty acid. It’s it’s butyrate. It’s it’s a product that is very relevant to formulations for gut health, and there are a number of there are a number of products that are coming together for gut health in the industry and Boolie is involved in a lot of the work that goes into our partners in the peptide space that’s emerging now, and that they’re showing very strong interest not only in arbuterate, but a particular stack that we’ve done with buterate, which is two molecules in one cyclodextrin cavity.

Dynamic Atomization: A Gentle Approach to Advanced Powder Processing

William: It’s buterate and n acetylcysteine stacked together. It’s a one of the patent patents we have is around stacking two molecules or more in one cyclodextrin cavity. Tesseract was the first to do that and show the synergies that we can extract from multiple molecules in one cyclodextrin cavity. But the butyrate molecule itself is extraordinarily volatile. Butyrate is one of three key short chain fatty acids, so you produce that yourself in your gut when you’re you’re breaking down fiber. And that particular biologic drives more than 300 key processes in the body. But because of its volatility, that raw material oxidizes extremely rapidly, and so it has almost no shelf life. What we’ve shown in our stability testing is that we can make that product last for years. The potency testing on that product far exceeds the three year shelf life that we put on our finished powder.

William: That’s one example where we’ve taken a product that has virtually no shelf life, and I mean, three months or less in raw material form to something that has years of potency sustained once it’s reacted with our technology. The second one is one of the original one of the original peptides.

It’s become quite well known and quite popular, which is glutathione. Uli’s smiling because it’s one of her favorite ingredients. Glutathione is something that is produced by each person’s liver in small amounts. I wish we all produced more of it. The more we produce, the more we can slow the aging process because glutathione neutralizes toxins in the body. It seeks out reactive oxygen species. It attaches to free radicals and prevents them from doing damage in the body because they attack other items in tissue and destroy tissue.

William: And so if we had more of it, we could counteract that damage more aggressively in the body. It’s one of the original. It’s a tripeptide. And so what’s also interesting about this particular structure is that we have amazing data to show particularly how powerful it is with our delivery technology. In its raw material form, it’s unabsorbable by the body. If you take glutathione in oral form, it’s fortunate for a person to move the needle one or 2%. That’s about all the benefit you get in blood plasma blood plasma readings over time.