“Cellular longevity and healthspan are exploding into a mega-category, and the only way to address these properly is with targeted advanced delivery systems,” Kokkinis told NutraIngredients. “The reason for this is that the hallmarks of aging are mainly at the cellular level. You will need help to transport your active molecule to the place that it needs to be in the cell (e.g., mitochondria, nucleus, etc.), and the only way to do this is with delivery systems. However, you need to be cautious of not one system can address all active ingredients. All systems have their pros and cons.”
Pharmako, which has had a strategic partnership with Gencor/Saanroo for many years, was founded by Kokkinis, formerly a senior manager at Australian regulator the Therapeutic Goods Administration, and ex-Swisse Wellness executive Eric Meppem in 2015—the same year it launched its multi-award-winning AquaCelle technology.
The company has since expanded its portfolio to include a range of innovative delivery technologies, all of which are used in over 100 products and in over 50 markets worldwide.
While Pharmako has clinically studied a finite group of ingredients, the opportunity for advanced delivery systems is far greater and endless, Kokkinis said.
“Terms such as, GLP1, dysbiosis, cellular longevity, NAD+, NMN, mitochondria, Akkermansia, Hallmarks of Aging, etc. are all fairly new in our industry and have only come about in the last few years. The ingredients that address these are pretty much the same ingredients that have been around for the last 10 to 20 years. The only difference is that different ways need to be found to address their ability to act effectively on the above ‘categories’,” he said. “This is where advanced delivery systems come into play.”
Options
Pharmako offers four distinct technologies that can be applied to a wide range of active ingredients and formats, Kokkinis said.
Micellar (AquaCelle)
The first technology developed by Pharmako, AquaCelle is a Self-Micro-emulsifying Delivery System (SMEDS) that forms micelles when it comes into contact with a watery environment (e.g., the gastric juices), he explained.
“Under these conditions, it instantaneously encapsulates the liquid lipophilic active ingredient forming a colloidal solution that is easily absorbed by the body. AquaCelle is designed to work with liquid lipophilic active ingredients (e.g., omega-3s, evening primrose oil, vitamin E, vitamin D3, astaxanthin, etc.).”
The first of over 10 Pharmako human clinical studies was conducted on AquaCelle coupled with CoQ10, which showed an increase in blood plasma absorption of over 300%.
Solid Lipophilic dispersion (LipiSperse)
LipiSperse is a coating technology used with solid lipophilic active ingredients, Kokkinis said.
“When the LipiSperse coats the lipophilic powder, it creates a hydrophilic surface, which allows the powder to easily disperse in water,” he explained. “This dispersion increases the surface area of the powder, which then gets absorbed by the body. LipiSperse has over 20 published studies and has won multiple international awards.”
LipiSperse has been applied to a range of popular active ingredients, including curcumin, resveratrol, PEA, quercetin, berberine and OEA.
Liquisolid carriers for lipid based systems (CPO)
Liquid formulations face several challenges in terms of stability, handling and ease of use. Solid dosage forms (such as tablets and capsules) are preferred due to their ease of administration, production and packaging.
Kokkonis said that novel techniques, like Pharmako’s CPO liquisolid system, can overcome these challenges by converting oil- and liquid-based formulations into stable, solid powders suitable for tableting or capsule filling.
Typical oil to CPO loading is 50:50 but it is not unusual to get a 65:35 loading. Oils currently commercialized with the CPO technology are: French lavender oil, astaxanthin, lutein, beta-carotene, Manuka honey, ginger oil and omega-3s. Also, AquaCelle can be coupled with the CPO format to give an even better absorption profile, Kokkinis added.
Liposomes and proliposomes (PlexoZome and PlexoZome Pro)
Discovered in 1964 by hematologists Alec Bangham and R.W. Horne, liposomes are tiny, spherical, engineered, nanostructures that mimic the body’s own natural cell membranes. These specialized delivery vehicles offer a wide range of advantages, from targeting specific tissues or cells to protecting encapsulated agents from metabolic digestion, resulting in better absorption and efficacy of ingredients.
“In general, liposomes can only carry a small amount of active ingredient,” Kokkinis said. “For hydrophilics, you can achieve a maximum of around 20%, and for lipophilics, you are doing well to get around 1%. Seeing formulations claiming a 70% concentration of vitamin C is a giant red flag; as is a 10% loading of curcumin, for example.”
Liposomes presented as powders should also be taken with caution, he said, because true liposomes require water to maintain their circular, bi-layer structure. Removing the water (by spray drying, for example) creates a dry phospholipid ball that crumbles apart, he added. Also, the high temperatures involved in spray drying tend to destroy these structures and the actives.
“Pro-liposomes are powders that are an exception,” Kokkonis noted. “Pro-liposomes contain the usual ingredients that make up a liposome (plus some other specific ingredients) that once they are introduced to water (hydrated) they spontaneously form a liposome.”
Boosting bioavailability
“It is hard for the brand companies to differentiate from one another, and the only way to achieve this is by having an advantage over their competitors,” Kokkinis said. “The advantages we offer are better absorption, clinically studied and customized formulations. That is, you don’t have to pick one of the thirty ingredients that we have already commercialized, but you can come to us with your favorite ingredient, and we’ll offer you a solution to make it better. This is what makes us individual and interesting. We only want to make interesting products.”
Advanced delivery systems can enhance bioavailability, and the market has witnessed different ingredient players race to one-up the competition. One prime example is the curcumin space, where suppliers launched ingredients claiming ever higher bioavailability boosts. Such claims confuse the market and consumers, according to Kokkinis.
The problem with these ‘X factor’ claims, he said, is that nobody gives any detail on the physical characteristics of the comparator ingredient or what, if any, dose response study they conducted.
“When you look at the absorption of the actives into blood plasma, you can get figures that are nonsensical,” he added. “The reason for this is because absorption is hardly ever linear . That is, a 500 mg dose of curcuminoids does not necessarily yield a doubling of the effect of a 250 mg dose or quadrupling the effect of a 125 mg dose.”
Pharmako has never promoted a “more is better” approach, he added. “On the contrary, we totally promote the “less is better” model. It all comes back to what the increase in blood plasma levels are. This is what is important regardless of how you get there.
“Let’s say for example, from the literature, a dose of curcuminoids to reduce inflammation is 375 mg/day taken orally. Let’s also say that published studies have shown that this oral dose of curcuminoids will increase blood plasma levels to 100 ng/ml. Now, assume we had an advanced delivery system coupled with the same dose of curcuminoids and achieved an increase of 800 ng/ml. This would mean that we could reduce the dose of the curcuminoids significantly and still have the same effect.”
