Sebastian Balcombe

The myriad types of dietary supplements you can recommend or carry in your line can be dizzying. One question that tends to arise is, “how do I ensure that my client is receiving the nutritional ingredient in a way that is optimally absorbed, and more importantly, does the increased absorption through the small intestines into the blood lead to higher absorption and better performance at the target tissue?” Liposomes are the answer. But the quandary lies in what truly constitutes a liposome.

A liposome is a lipid protective coating that encases the active ingredient. A true liposome is a precision-oriented structure that is capable of delivering bioactives (vitamins, minerals, plant compounds, peptides, fatty acids, and more) into the bloodstream where they can reach their targets in higher concentrations—with greater bioactivity and ultimately better performance.

Liposomes Defined

A concise, technical definition of a liposome is “a tiny sphere-shaped structure with an aqueous core and at least one lipid bilayer that can be filled with a water- or fat-soluble active ingredient.” There are several liposomes marketed in the nutraceutical industry that are typically in liquid form. This dramatically limits both their application as well as the ability to control the size of the liposome.  And size is a critical factor for both solubility and intestinal permeation, two of the major factors for optimizing bioavailability.

The clearest way to think about liposomes is how the body naturally prefers to absorb nutrients—with a lipid wrapped around a nutrient for protection when it reaches the small intestine. This arrangement enables the nutrient to penetrate the epithelium of the small intestine for intact delivery into the bloodstream. The nature of a liposome is to optimize nutrient absorption through the GI tract, increasing its concentrations in blood plasma and increasing bioavailability in the target tissue.

Liposomes enrobe and protect the nutraceutical ingredient (or blend) to ensure it shuttles through the small intestine and the actives are released into the blood and then into the tissue. Key point:  the liposome delivery system with the active ingredient within is more bioavailable than the ingredient itself. The liposome allows the active ingredient(s) it contains to be delivered to the target inside the body.

While not absolute, generally speaking, liposomes work best for ingredients that are very fat-soluble, or very water-soluble. Therefore, they can work very well for extremes on both ends, but again, there are no exact rules. Sometimes we’ve seen unexpected results with a variety of ingredients with different polarities and molecular weights.

Know the Differences: Why Validation Counts

While liposomes appear rather simplified in their structure, there are major differences that separate ineffective or unintended-impostor liposomes from true liposomes. Bottom line: Not all liposomes are created equal! Actually, most “liposomal” ingredients, when tested, are not even liposomes to begin with, i.e., ZERO liposomes! When we talk about making liposomes much better than anything in the industry, we need to address the reality that most ingredients marketed as liposomal, when tested, are found to have no liposomes whatsoever.

Liposomal creation typically begins with a source of phospholipids, e.g., sunflower oil, soybean oil, and others, which yields a variety of phospholipids (such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine) and these are used to structure a basic sphere. But there is more to the creation of liposomes than just the phospholipids. Here are some of the key characteristics of a true liposome:  

• Have a well-defined bilayer and have smooth core surface
• Be nano in size
• Be evenly distributed
• Have an optimal zeta potential correlating with improved stability and decreased possibility of leakage of the bioactive inside

Many conventional “liposomes” are not true liposomes. When examined using a high-powered Cryo Transmission Electron Microscope (CryoTEM), many, if not most, contain no bilayer, meaning they are either a micelle, an ingredient wrapped in a single phospholipid layer, or they are neither micelle nor liposome, meaning they have no protective layer. Zeta potential is another crucially important part of a liposome one needs to understand. “Zeta potential” describes how tightly the liposome is holding onto the ingredient(s) packaged within. A poor or high Zeta potential shows that the liposome is unstable, weak, and can break apart before it reaches its destination. A viable liposome needs a sturdy, resilient encapsulation that provides protection against degradation from gastric acids and other materials within the GI tract.

Zeta potential in the approximate range of -30 to -60 meV is optimal and reduces the possibility of leakage of the active ingredient, and improves stability during manufacturing, on the shelf, and in the body. Zeta potential values are measured to confirm a strong encapsulation of the active ingredient and stable colloidal suspension.

Additionally, there are other key criteria that define an optimized liposome. The size of the liposome needs to be between 100 and 200 nanometers to be optimally absorbed by the small intestine. There are a few exceptions when the bioactive inside cannot be nano size–as in the case of Vitamin B12. A test that can discern the average size of the liposome and validate its stability is Dynamic Light Scattering (DLS) analysis. Using LipoVantage® Liposomal NMN as an example, DLS shows that its particle sizes are approximately 175.3 nanometers. The smaller particle size fosters better bioavailability and results in a more stable colloidal suspension.

A true liposome is also spherical, as validated using Scanning Electron Microscope (SEM) testing; and must be well-dispersed and leakage-free, as seen through Cryo Transmission Electron Microscope (CryoTEM) testing. 

Testing liposomes is a specialty and the instrumentation, such as CyroTEM and SEM, is very expensive. These tests are performed with highly expensive equipment in a specialized material science lab — not all companies that create liposomes do this. Relationships with universities that specialize in liposome analysis drives both reliability and innovation in this delivery form.

A Distinctive Liposome: The Power of Powder

The basic question is — if the core of a liposome is liquid, how can you create a powder liposome? Not all liposomes can be rendered into a powder. This takes extraordinary expertise and our patent pending LipoVantage® formulation. Through our proprietary process, we can gently but effectively dehydrate the liposome so that it and its contents remain intact, while maintaining the water loving hydrophilic polar core. It may sound counterintuitive, that this would collapse the liposphere, but this is where scientific advancement comes in. DualHydrogel™ Technology uses a proprietary blend of natural polar ingredients. These polar ingredients are both in the core of the liposome and surround the liposome sphere to prevent potential collapse during the dehydration process, thus maintaining the true liposome bilayer. This technology also enhances stability in the body and improves bioavailability.

As an example, think of a small, deflated balloon with a polar (hydrophilic-water loving) compound at the core. When put into water, a small amount of water can permeate the balloon’s membrane, and the polar core dissolves into the water, causing the balloon to swell and increase in size and keep the water inside its core with the lipid bilayer surrounding it.

Our powder liposomes are like that balloon that has been shrunk down but still has the polar characteristic in its core, and once it comes in contact with water (gastric fluid and intestinal fluid or when put into a water drink mix), the polar core of the liposomes absorbs the water and become a larger liposome. The 100-200 nm size mentioned above are our liposomes that have absorbed water and are at full size, not the dehydrated much smaller powder liposomes.

The beauty of powder is that it provides much more control of the size of the liposome in contrast to the liquid form. That is not to say that one is better than the other. It is what is most suitable for the application and the specific ingredient(s) within. While many liposomes are limited, LipoVantage® is versatile and can be used effectively in not only tablets and capsules but also in gummies, chews, functional foods, RTDs and more. The technology can even be used for topicals, creams, and lotions. This is important since a significant number of your clients are pill-fatigued and are interested in these other delivery systems.

Research: Proven Effectiveness

LipoVantage® was put to the test with vitamin C. In a recent randomized, double-blind, placebo-controlled study (conducted in 2023, not yet published), we looked at absorption and bioavailability at different time points. We found that there were higher levels of LipoVantage® vitamin C in leukocytes, 20% more than non-liposomal vitamin C. This shows that the vitamin is getting to its target at much higher levels. Note that having a higher level of vitamin C in the blood does not automatically mean it is getting to where it needs to be. It’s important to know that the vitamin C is actually making it to the leukocytes.

In another test, a fasted and fed intestinal in-vitro model, LipoVantage® vitamin C powder was shown to be 1.4 times more stable in the small intestines than non-liposomal vitamin C; Vitamin C is unstable in the 6.8 pH of the small intestine. The stability of a 500 mg dose of vitamin C as ascorbic acid was tested in simulated intestinal fluid for 2 hours, comparing non-liposomal USP vitamin C against a competitor liposomal vitamin C and Specnova LipoVantage® vitamin C.

Published January 27, 2024

About the Author

With over twenty-five years in the natural products industry and a Master of Science in Medicinal Chemistry, Sebastian Balcombe approaches natural ingredients and delivery systems discovery and development through the lens of an experienced entrepreneur and scientist. From in-silico computational chemistry for compound discovery to clinical research and IP development, he has developed over thirty nutraceutical ingredients, multiple liposomal and beadlet delivery systems as well as the IP surrounding them.

With his in-depth understanding of liposomal technology, Sebastian’s most recent research has focused on how this novel delivery system works with natural ingredients, including the ability to increase the bioavailability and stability of critical nutrients in the body. Sebastian’s authentic passion, craftsmanship, and commitment to creating a superior customer-brand experience have built his reputation as a pragmatic perfectionist in the industry. He is dedicated to helping people achieve a better quality of life and is committed to establishing new standards in product development, innovation, research, and quality control.