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Dr Christopher Shade: Liposome researcher

 
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What got you interested in researching heavy metal toxicity, in particular mercury toxicity?

I was doing research on pollution in streams in agricultural areas for my Masters Degree and went to the University of Illinois to interview with professors there. The guys I met were pretty boring but they put me in to meet a guy name Robert Hudson who did modelling of global mercury cycles and he was quite fascinating. He asked if I could design a new mercury speciation system and I say, "Sure!" I didn't even know what it really meant but I knew I was good in the lab. While working on that one day I had this heavy realisation of how much mercury was coating my mouth and dripping through my GI tract. 

Though my focus in grad school was environmental mercury chemistry, as soon as I left school, I started moving toward clinical chemistry.  

How long did it take to develop the liposomal technology?

I had other people making my first versions for me, but I was never satisfied with what they had done. I started working on it myself and was fortunate to meet a guy in Boulder who gave me a bit of direction and I quickly made some good breakthroughs. It was probably two years until I started offering my own. I have been obsessed with it ever since.

What are the features and benefits of liposomes compared to conventional forms of supplementation?

The most basic benefit is the quick and efficient uptake of liposomes gives you higher peak blood levels and higher total absorption. For many compounds, it is the peak levels that cause effects through mechanisms like gene upregulation; this can be the difference between a great response to a therapy or just spending money on fancy ingredients.

Deeper levels of  benefit include the potential for higher blood-brain barrier penetration and enhanced cellular penetration. This area is growing rapidly in understanding of the abilities of liposomal deliveries and ways to modify the particles to gain different effects.

What are the differences between a liposome, a micelle, emulsion and nano-emulsion?

All of these terms relate to the use of surfactants dispersed in water solutions. Surfactants have water loving (hydrophilic) and water fearing (hydrophobic) sides.  As such, surfactants are useful for dispersing oils into water by arranging themselves at the interface of the oil and water (i.e. usually on the surface of an oil droplet that is dispersed in water). When oils are dispersed into water the surfactant stabilises the oil droplet and shields it from joining with other droplets (coalescing). These stabilised droplets of oil dispersed in water is called an emulsion. 

When these emulsions are placed under large shear forces (high pressure homogenisation), the droplets are reduced in size. If the size of the droplets is reduced to under 100nm, the resulting emulsion is called a nano-emulsion.  At this size the emulsion is more stable than larger emulsions because the brownian movement effects (random vibration of particles in water) is greater than the effect of gravity that would usually push the oils to the top and the water to the bottom. 

Lecithin is a type of natural surfactant that is derived typically from seed oils and is composed of the same components (mostly phospholipids) that cell membranes are made from. Phospholipids purified from lecithin are very useful surfactants because of 1) their therapeutic use for rebuilding our cell membranes and 2) their natural ability to form structures called liposomes when dispersed in water. Phospholipids can also be used to stabilised emulsions of oils. Lecithin, the crude source for the purified phospholipids, is used to keep fats from separating from foods, and is best known for its use in emulsifying cocoa butter with milk and cocoa solids in making chocolate.

A liposome is a sphere with a water-based core, and made of a phospholipid bilayer.  

A micelle is a particle of surfactants dispersed in water with the hydrophobic "tails" pointed inward and the hydrophilic "head" pointed outward toward the water. Oil-soluble compounds can be dissolved in the inner hydrophobic core of the micelle. Soap dissolved in water forms a classic example of a micelle and the micelle is what is responsible for soap removing oils from surfaces by dissolving the oils in the core of the micelle.

An emulsion is a dispersion of oil in water that is stabilised with an surfactant (emulsifier).

A nano-emulsion is an emulsion with oil droplet size below 100nm.

The term lipid nanoparticle refers to any of the above particle types, or hybrids thereof, that have been reduced to sizes below 100nm.

A phytosome is a proprietary term for blends of phospholipids and plant compounds such as milk thistle. These are really admixtures and have not be preformed into particles. The manufacturer of these formulas relies on particles being formed in the gut. The manufacturers literature implies that there are discreet particles and that the phytochemicals (silymarin, curcumin etc) are chemically bound to the heads of the phospholipids, but this is not true. When phytochemicals such as EGCG are added to dispersions of liposomes, they do associate with the hydrophilic heads, but in the phytosome formulations, the phospholipids are just mixed with the phytochemicals and left to spontaneously form particles and associate with the phytochemicals in the GI tract. There is an enhanced GI uptake from their association, but the system is not as sophisticated as it is portrayed.

Deeper levels of benefit include the potential for higher blood-brain barrier penetration and enhanced cellular penetration. This area is growing rapidly in understanding of the abilities of  liposomal deliveries and ways to modify the particles to gain different effects.

Why and who should take liposomal supplements? Are there particular population groups/conditions who should be considered?

Everyone can benefit from the rapid and high absorption, though groups with compromised GI absorption absolutely need enhanced absorption methods such as these. 

What direct benefits can patients see/feel from liposomal technology? 

CoQ10 and B12 are especially compelling in the immediacy of their effect; they really bring up the mental and physical energy and brighten the mood.

Is it an issue that nano-sized particles can be delivered to parts of the body where they should not be delivered?

Nanotechnology is a very broad area that comes under a umbrella of size designation (nanotechnology is generally defines as less than 100nm). For solid particles of mineral forms, such as titanium dioxide or zinc oxide, there is a real dangers as these particles are not meant to be in the body and can be strong free-radical generators. For lipid nanoparticles, the story is very different. The liposomes are made of the same materials that cell membranes are made out of and those components are used by the cells to generate their membrane. Additionally, the particles are very similar to how the body moves dietary fats. Particles called chylomicrons are made of bile salts, phospholipids, and dietary oils and are in the 50-200nm range, very similar to the liposomes and nano-emulsions we use.


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