Liposomal Delivery Increases Bioavailability by up to 1,500%
Adapted from PC Liposomal Encapsulation Technology
by Robert D. Milne, MD, Life's Fountain Books, 2004
High tech encapsulation technology is proven nanochemistry that can make health and longevity supplements 10 to 15 times more efficient and effective. The medical research world is abuzz with excitement about a host of bio-technologies that promise to improve health and extend life.
Even as you read this page, new products are being formulated that promise to improve health and increase longevity.
A Little History
Liposomes were discovered by Alec D. Bangham in 1961.i Liposomal Delivery (LD) has been in the developmental stages since the 1970s. For the first 25 years or so, it was employed almost exclusively by medical researchers who needed to deliver particular drugs, dyes or other therapeutic agents to specific tissues; from that time until the present, only a handful of companies have used LD in nonmedical applications.
Because of its superior transdermal transport qualities, a few companies have been using LD in some of their topical moisturizers, cell therapy and anti-aging cosmetic products. An even smaller number of companies are now using LD for the oral delivery of dietary supplements. Given the impressive benefits of LD, we anticipate increasing numbers of supplement companies and supplement products employing liposomal delivery encapsulation very soon.
Why Is LD So Powerful?
The basic reason that LD is so powerful is that it enables the delivery of more pure, non-degraded, substances to the specially targeted tissues and organs than any other method. In most cases, LD is so efficient that dose levels can be 10 to 15 times smaller. Reductions of this magnitude have tremendous therapeutic and economic implications whether the substance to be delivered is a drug or a dietary supplement. In addition, the essential phospholipids used to make the liposomes that encapsulate the nutritive substance have health benefits in and of themselves. Another factor is the human digestive system itself. Enzymes in the mouth and stomach, digestive juices, bile salts (to neutralize the digestive acids), and various flora in the intestines can further degrade the supplement or drug. These endogenous substances and organisms can also hinder uptake of food, food supplements and drugs in the intestinal tract. Because the digestive system is seldom empty, interactions between foods, other supplements or drugs can also reduce, degrade or alter the desired outcome.
LD encapsulation protects substances from most of the degrading and inhibitory factors mentioned above by providing unparalleled payload protection.
LD utilizes phospholipid liposomes to form a barrier around their contents that is resistant to digestive juices, alkaline solutions and salts found in the human body as well as free radicals. Because of this, they do a superior job in protecting the contents from oxidation and degradation from external substances and conditions. Most importantly, this protective barrier stays intact until the contents have been delivered to the system, organ, gland or cell where the contents will be used.
A myriad of liposomes have been developed. Some release their contents at a certain temperature, others at a specific pH, while others do so in the presence of other substances. They function like microscopic smart bombs that can travel through the body and deploy their payload to the desired location.
Factors That Affect Bioavailability
The bioavailability of tablets and capsules can be drastically reduced before they are ever placed in the mouth.
Factors that degrade most supplements include:
- Moisture, oxygen and other factors in the environment
- Enzymes and digestive juices in the mouth and stomach
- Bile salts in the intestines
- Friendly and unfriendly organisms in the intestines
- Food and drug interactions in the digestive system
- Additives, coatings, binders, fillers, sugars, colors and flavors added to enhance packaging or facilitate swallowing
- Incomplete assimilation due to partial or non-breakdown of tablet or capsule into small enough particles for uptake in the intestines
Another quality of LD that makes it so effective is found in the very makeup of the encapsulating liposomes. Most LD liposomes are made with essential phospholipids. The body requires these phospholipids in order to grow and function. In fact, every cell in the body has a protective membrane made from phospholipids.
When phospholipids are consumed, they are utilized to replace damaged ones, making cell membranes throughout the body healthier and better able to protect and nourish the cells they encase. The importance of phospholipids is so great that, in some cases, the encapsulating liposomes in liposomal products may actually provide more health benefits than the substances they carry. Finally, their submicroscopic size and chemical structure is recognizable as a friendly substance to the body, meaning that they can navigate through the digestive, lymphatic and circulatory systems with ease. This is in contrast to some supplement tablets, pills and capsules that may be eliminated in the stool partially digested or totally intact.
The Phospholipid Miracle That Makes LD Possible
Liposomal Delivery Technology (LDT) is a unique method of making submicroscopic bubbles – called liposomes – which are used to encapsulate various substances. The liposomes used in LDT are made from phospholipids. To appreciate LDT fully, a brief explanation of their biochemistry is necessary.
Phospholipids are the basic building block of every cell membrane in the human body. How they work and form membranes is elegant and miraculous. Each phospholipid molecule has three major parts, one head and two tails. The head is made from three molecular components: choline, phosphate, and glycerol. The important thing to remember here is that the head is hydrophilic, i.e., attracted to water. The tail is a long fatty acid chain. These fatty acid tails are hydrophobic, i.e., repelled by water.
When phospholipids are put into an aqueous (water-based) solution, the hydrophilic heads of the lipids form a line side by side with their tails behind much like swimmers at a starting gate. Because the tails are hydrophobic, another phospholipid layer will line itself up tail-to-tail in response to the same aqueous environment. This natural alignment creates two rows of tightly packed phospholipid molecules, called a phospholipid bilayer. It is these phospholipid bilayers that form the membranes around and within every cell in our bodies. One bilayer is about one thousandth the thickness of a piece of paper.
In the human body, phospholipid bilayers form the outer cell membrane by arranging themselves in a spherical shape with the heads of the phospholipids making up the external and internal surfaces of the cell. This holds the contents of the cell in and protects them from harmful substances on the outside.
A combination of different proteins interspersed within the phospholipid bilayers in every cell provides channels for allowing nutrients in and cellular waste products out as well as providing intercellular communication. With millions of phospholipid molecules required for each cell membrane, the number of these molecules is almost incomprehensible. Phospholipids literally enable life as we know it by making it possible for cells to exist.
Later we will learn that there are different kinds of phospholipids. Some phospholipid compounds are synthesized in the liver. Other phospholipids, such as phosphatidylcholine (pronounced FOSS fah tie dal KO lean), are essential for life and health but cannot be made by the human body. These are essential phospholipids which must be derived from the diet. The difference in form and function between the different phospholipids is determined by the composition of the two fatty acid tails attached to the choline-phosphate heads.
Phosphatidylcholines are made from polyunsaturated fatty acids. In most LDT food supplement applications, it is these essential, polyunsaturated, fatty acid phospholipids that are used to create the liposomal capsules.
The Most Powerful Phospholipids
Although the name phosphatidylcholine can be very intimidating the first few times that you see it, its inclusion in our discussion of liposomal encapsulation is essential if we are to fully appreciate the significance of LDT. In the future we will refer to phosphatidylcholine as PC.
What is PC?
As mentioned above, PC is a special class of essential phospholipids. As discussed previously, phospholipids are composed of a hydrophilic, phosphated choline head and two hydrophobic fatty acid tails.
Fatty acids are organic acids made from chains of carbon and hydrogen atoms that form the building blocks for lipids, oils, and waxes. Essential fatty acids are required for cell membrane synthesis and fat metabolism.
There are a host of fatty acids in our foods and in the human body. Linoleic acid and gamma-linolenic acid, however, are the only essential fatty acids. These acids are absolutely required for growth and health but cannot be synthesized in the human body; they must be supplied by the food we eat. PCs are a smaller subset of essential phospholipids.
Not All PC Is Created Equal
As discussed above, PC is a type of phospholipid that has two essential fatty acid tails. Fatty acids can be saturated or unsaturated. Thus there can be a substantial difference in some important qualities of different PCs based upon the saturation level of the two fatty acid tails.
The Value of Unsaturated versus Saturated Fatty Acids in PC
Saturated fatty acids are chains of carbon atoms joined by single bonds, which allows each carbon atom to bind to a maximum (saturated) number of hydrogen atoms. In an unsaturated fatty acid, some of the carbon atoms are attached to one another with double or triple bonds. Each double bond eliminates one hydrogen atom, and each triple bond eliminates two hydrogen atoms from the chain.
In addition, each double or triple bond creates a bend or "kink" in the fatty acid chain. The physical properties of fats, oils, and fatty acids can change substantially as the chains become more unsaturated.
The difference between saturated and unsaturated fats is so dramatic that it can be see with the naked eye. Lard, butter and bacon are examples of saturated fats. Because of their straight carbon chains, the chains lie very close to one another. They easily solidify at room temperature and are more viscous (sticky, thick, slow to flow).
Unsaturated fats (like vegetable oils) have bends in the carbon chains; these fats are usually liquid at room temperature and non-viscous (slippery, thin, easy flowing). Fats and fatty acids that have a high number of double and triple bonded carbons are called polyunsaturated.
Just as the physical and chemical properties of saturated, unsaturated and polyunsaturated fats, oils and fatty acids are varied and profound, so is the difference in PC with polyunsaturated fatty acid tails.
The benefits of LDT enumerated here assume the use of polyunsaturated PC in the preparation of liposomal encapsulation products. All the studies and research regarding the use of essential phospholipids and PC cited were accomplished using polyunsaturated PC.
Integration of Polyunsaturated PC into the Body
Although there is much yet to be learned about the specific mechanisms of PC integration and metabolism in the body, there is much we do know.
Observations using radioactively tagged fatty acids in PC demonstrate that polyunsaturated PC quickly replaces the more saturated and/or damaged phospholipids in plasma membranes. This exchange accomplishes many important tasks.
The polyunsaturated fatty acids quickly begin to facilitate the metabolism of low-density lipids and cholesterol. This gentle "degreasing" scrub is manifested throughout the body.
As a result, life giving blood moves through the circulatory system more quickly and easily, especially in the tiny capillaries, as the blood becomes less viscous (less thick and sticky) and deformable (able to change shape).
Plasma membranes return to a more efficient, more fluid state, and hardened saturated fats and cholesterol that have become lodged there are removed and metabolized.
Cells throughout the body become more able to resist the damaging effects of free radical attack.
The heart, pancreas and liver become energized as their work becomes much easier.
Choline levels increase in the brain, which has many positive implications for proper mental function and helps maintain and improve memory.
Optimizing the Power of PC Liposomal Delivery Technology (LDT)
The Structure of Liposomes
PC liposomes are an integral part of LDT. They are the spheres or vesicles that encapsulate the supplement (payload) to be delivered.
Liposomes come in many sizes and structures. The size of a liposome is determined to a great extent by the process used to make them. Diameters can range from hundreds of micrometers (one-millionth of a meter) to under a hundred nanometers (one-billionth of a meter) or smaller.
The liposomal structures are also largely dependent upon the method of preparation. They can be uni-lamellar (single layer), bi-lamellar (double layer) or multi-lamellar (multi-layer).
Bi-layer liposomes provide the best combination of protection and efficiency. Liposomal efficiency (a ratio of payload mass to liposome mass) increases with the size of the liposome which may be a consideration in some LDT applications.
In general, however, smaller liposomes are much more able to protect the payload and navigate within the human body than larger ones. In addition, the smaller the liposome, the longer the shelf life, and the greater the stability of the liposomal structure.
Biochemical Makeup of Liposomes
Glycerophospholipids are used to make liposomes. Most LDT used for food supplements employs a particular type of glycerophospholipid called phosphatidylcholine, which can be extracted from certain animal proteins, egg yolk, sunflower lecithin, or synthesized in a laboratory. For food supplements, PC from sunflower lecithin seems to be the best liposomal lipid.
There are at least five preparation method types used to prepare liposomes. The only method type of importance here is the mechanical type. Mechanical methods employ machines or devices to cause the formation of liposomes as opposed to the use of chemical or environmental agents.
Most mechanical preparation processes can be classified into one of three categories: extrusion, sonification and microfluidization. Extrusion forces the liposomal material through a grate (usually a polycarbonate membrane). Sonification uses sound waves to agitate the liposomal material into a spherical shape. Microfluidization uses a device called a microfluidizer, which forces the material against a forming plate at an extremely high pressure. The impact causes the formation of extremely tiny vesicles – the smallest liposomes of any method.
As with all chemical compounds, liposomes will eventually decompose. Over time, liposomes are subject to oxidation, hydrolysis, and aggregation. To a degree, having a liposomal size under 200 nanometers will provide increased stability and protection.
Optimal Conditions for LDT
- Size: Under 200 nanometers
- Structure: Bilayer
- Composition: Phosphatidylcholine
- Source: Sunflower (non-GMO, organic)
- Storage Temperature: Room temperature or below but above freezing
- Storage: Air-tight, light-tight container
- Ingestion: 10 to 15 minutes prior to a meal
Observed Health and Anti-Aging Benefits of Polyunsaturated PC (Essential Phospholipids)
PCs have been shown to have a number of health benefits, including:
- Reduction in total serum lipids (fat in the blood)
- Reduction in LDL (bad) cholesterol
- Increase in HDL (good) cholesterol
- Lowers serum triglycerides and overall cholesterol
- Reduction in triglycerides
- Reduction in cholesterol deposits in vascular walls
- Reduction in blood platelet aggregation (detrimental tendency of blood cells to stick together)
- Effective anti-oxidant in lipids
- Increase in red blood cell fluidity
- Reduced viscosity
- Improved coronary circulation
- Increased exercise tolerance
- Improved peripheral circulation (hand and feet)
- Liver protection and rejuvenation
- Improved immunity
- Improved memory
- Prevention of excess collagen formation and cross-linking (wrinkles and scarring)
PCs are present only in small amounts in liposomes that are probably not great enough to constitute supplementation. These benefits do, however, point out the safety and beneficial effects of PCs.
Clinical Use of PC in LDT
Since the 1970s when liposome technology was first developed, PC liposomes have been used in a number of liposomal drug delivery systems.ii They have been used to improve solubilization, site-avoidance (for substances that could cause unwanted damage to organ systems), sustained-release, drug protection, RES targeting, specific targeting, extravasation (release of fluids into tissues from blood vessels), accumulation, enhanced penetration and drug depots. Liposomes have been particularly useful for topical applications of drugs and cosmetics. For drugs, topical liposomal preparations reduce serious side effects due to high absorption of the drug, significantly increase the accumulation of the drug at the application site, and readily incorporate a wide variety of both hydrophilic and hydrophobic drugs.iii Liposomes have also proven very effective as one way to target drugs, nutraceuticals and other payloads in the gastrointestinal tractiv. Nutraceuticals have been packaged in liposomes to increase their absorption and reduce digestion in the gastrointestinal tract. Curcumin, a powerful antioxidant derived from turmeric that is poorly absorbed into the body, has been combined with PC to form what are called phytosomes that greatly increase absorption of the nutrient through the gut barrier, resulting in significantly higher blood levels than with standardized 95% curcumin alone.v
When colostrum is expressed from the mammary glands of mammals, the important proteins it contains are protected naturally by plasma membranes that are squeezed off from the secretory cells of the mammary gland. During processing, however, these globules of colostrum lose their protective coating and if not replaced, the contents will be exposed to digestive enzymes and acids in the gastrointestinal tract that will digest and degrade them, lowering their effectiveness greatly. By replacing the lost membranes with PC liposomes, the colostral proteins and other nutrients are protected from digestion and are able to reach their targets and retain their efficacy. That is why Colostrum LD has much greater efficacy than other colostrum without the LDT.
i Bangham AD and RW Horne, Negative staining of phospholipids and their structured modification by surface active agents as observed in the electron microscope, Journal of Molecular Biology 8:660-8 (1964).
ii Juliano RL, Liposomes as a drug delivery system, Trends in Pharmacological Sciences 2:39-42 (1980).
iii Egbaria K and N Weiner, Liposomes as a topical drug delivery system, Advanced Drug Delivery Reviews 5(3):287-300 (1990).
iv Pinto JF, Site-specific drug delivery systems within the gastrointestinal tract: From the mouth to the colon, International Journal of Pharmaceutics 395(1-2):44-52 (2010).