TL;DR

Will West, Tesseract‘s co-founder and CEO, says liposomal delivery has a strong track record with supplement nutrients but starts a ticking clock once paired with fragile peptides. Cyclodextrin inclusion protects peptides, but only on a case-by-case basis and never as a cure-all. Chief Marketing Officer Ulli Lindauer explains that sodium caprate (C10) addresses a different problem: it temporarily opens the roughly 200 nanometer gaps between mucosal cells for about 30 to 60 minutes so larger peptides can pass.

• Liposomal delivery has been seen as the most successful approach for nutrients in powders, liquids and gel caps. Will West says pairing it with peptides starts a ticking clock with a very short fuse.
• Cyclodextrin technology cannot be used universally. It has been adapted case by case for hundreds of different molecules, and it will never be a cure-all for peptide fragility.
• Even after a peptide is stabilized, absorption still has to be addressed for gastrointestinal, oral or nasal delivery.
• Sodium caprate (C10) was traditionally a tablet excipient. It temporarily enlarges the openings between mucosal lining cells for about 30 to 60 minutes and has been studied extensively for GLP-1s.
• Ulli Lindauer puts the openings between cells at roughly 200 nanometers. She says opening them 10 or 20 times wider lets a large variety of peptide sizes pass.
• Tesseract’s approach chains three tools: a cyclodextrin shell for protection and water solubility, an enzymatic release agent to open the shell, and the Capramax absorption and permeation enhancer.

Why are experts cautious about liposomal delivery for peptides?

Will West: They’ll have their unique and different approaches, of course. I picked liposomal out of the list in particular because the conventional wisdom in the broader supplement, nutraceutical and, I would say, health industry has been that liposomal delivery has been the most successful until recently in terms of facilitating the delivery of nutrients in a number of different ways: in powders, in liquids, in gel caps, for instance. There are certainly some good examples of how it has improved the general absorption of a number of ingredients in some of those situations. There are plenty of examples of how cyclodextrin technology can be used more effectively.

But the question here specifically about peptides is an interesting one because we’ve talked about how fragile peptides are, point number one. And secondly, how peptides, because of their fragility, have an extreme vulnerability to moisture and other types of exposure that undermine their shelf life. One of the weaknesses we see is that the market is trying to pair peptides with liposomal delivery in manufacturing. The problem with that is that as soon as you pair the liposomal technology with the peptides, you start a ticking clock. That’s actually a very short fuse.

So we generally start by cautioning people about using liposomal. It’s very common right now simply because people default to liposomal in a lot of cases. Liposomal gained popularity because there’s a belief that it facilitated the movement of things because of its lipid qualities. And that’s fine, but it simply doesn’t work when you have a fragile item like a peptide. Other coatings generally have a similar concern in that you can coat all sorts of things. But if you were coating something that’s very fragile, you have to be aware that the underlying product is still going to be vulnerable.

Where does cyclodextrin inclusion fit for oral peptides?

Will West: We’ve seen good results with the cyclodextrin technology. However, there is a nuance as to when and how the cyclodextrin technology can be used. It’s not something that can be used universally. There’s a history of the cyclodextrin technology being used on a case by case basis for hundreds and hundreds of different molecules that are adapted to those individual molecules. It looks as if, when the peptide industry grows, the same thing will happen. Formulations for use of cyclodextrin will continue to grow and adapt to that, and that’s what we’re specializing in and doing now.

However, there’s two sides of this. There’s the use of cyclodextrin to try to protect the peptide, but there’s still a need to work within the boundaries of the limitations of the peptide even once it’s protected, because cyclodextrin or any other technology will never be a cure-all for the fragility of the peptide. And secondly, once you’ve stabilized the peptide and enhanced its bioavailability to the extent that’s even possible on a case by case basis, you’ll still have to work to increase the absorption of the peptide if you’re trying to deliver it in the gastrointestinal system, in the oral microbiome, or across any other mucosal layer, like a nasal spray, for example.

So a complete portfolio of intellectual property that spans multiple delivery systems, intellectual property that covers both bioavailability and absorption, really has to be truly multidimensional and consider a broad range of platforms without undermining the core longevity and fragility of the peptide.

What is sodium caprate and why does it matter for peptides?

Ulli Lindauer: Sodium caprate has traditionally been used as an excipient in the pharma industry. It is waxy and tacky in texture, so it has been used a lot in tablets to make them compress really well and hold their shape. However, it’s also found to temporarily enlarge the openings between mucosal lining cells. If you think about your nasal mucosal lining or oral or gut wall, there is a small opening between the cells. That’s really the place where anything that you take orally specifically, or, let’s say, noninjected, has to pass through.

Sodium caprate, which is abbreviated C10, as well as a couple of other sodium derivatives, are able to open this small opening to a multiple of its general size for a rather short period of time, usually thirty to sixty minutes. And the cells will go back the way they belong without having any long term residual negative effects from that opening.

It’s been studied extensively for peptides, particularly the GLP-1s. The reason why this conversation comes up all the time is because peptides are exponentially larger than the opening between the cells. We have our own branded and patented sodium caprate. Sodium caprate gives us the ability to pair a peptide with Capramax, which is our branded ingredient, and open the tight junctions between the cells, let the peptide in, and then close them again.

How large are peptides compared with the gaps between cells?

Ulli Lindauer: The openings in general are roughly 200 nanometers.

That’s really tiny. There are plenty of natural ingredient molecules that are also tiny. For example, butyric acid is roughly 80 to 90. When you talk about peptides, you very quickly come to 5,000, 30,000, which is very, very large. So you can see that even if you open a 200 nanometer tight junction to, let’s say, 10 times or 20 times, it will let pass a large variety of different peptide sizes, and that’s fantastic.

You can swallow peptides all you want. If they cannot enter your system, if you cannot absorb them, then we talked about it earlier. Without absorption, there is zero bioavailability. With absorption, there is some bioavailability.

How do protection, release and permeation work together?

Ulli Lindauer: We deploy these technology platforms: the cyclodextrin to protect the peptide and make it fantastically water soluble, our enzymatic release agent to open the cyclodextrin shell, and our Capramax absorption and permeation enhancer to get the peptide through to the body. Now you have a way to address all the different challenges that a peptide presents, from its fragility to its size, in this chain that really delivers the peptide where it’s bioavailable.

Edited for length and clarity from a recorded conversation with Will West and Ulli Lindauer.