The fascinating world of liposomes

All that we talk about at PlantaCorp are liposomes. In our previous blog post, we probably piqued your interest about liposome-encapsulated ingredients as a better food supplement alternative. But how much do you know about liposomes? This blog post will explain more about their structure, manufacture, metabolism and associated safety concerns.

Liposomes: Man-made phospholipid bilayer spheres

In Greek, the word ‘Lipos’ means fat and ‘soma’ means body. The word ‘liposome’ therefore literally means a body of fat. What kind of fat molecule is very important to understand the working principle and advantages of a liposome.

Liposomes are specifically composed of phospholipids. Like fats, phospholipids are composed of fatty acid chains attached to a glycerol backbone. However, phospholipids have only two fatty acids connected to the glycerol backbone (diacylglycerol), while fats have three fatty acids (triglycerides). In phospholipids, the third carbon of the backbone is occupied by a modified phosphate group. A phospholipid thus has a phosphoglycerol group that comprises the ‘head’ and two fatty acid side chains. These can be saturated or unsaturated fatty acids and comprise the ‘tail’ of a phospholipid (1).

A typical phospholipid structure. The phospho head is composed of a phosphate group attached to one carbon of a glycerol backbone. This makes the head water-soluble. The lipid tail is composed of two fatty acid side chains (saturated depicted by the straight line, unsaturated depicted by the kinked line) attached to the glycerol backbone. This makes the tail water-repellent.

This composition of phospholipids is integral to their behaviour in water. Having a negative charge, the phosphate group makes the head hydrophilic (water-loving). The tails on the other hand, have no charge on them and are thus hydrophobic (water-repelling). Thus, when added to water, phospholipids will spontaneously rearrange into a single layer sphere called a micelle. In a micelle, only the hydrophilic phosphate heads are in contact with water.

A micelle versus a liposome. On the left is a micelle composed of a single layer of spontaneously arranged phospholipids. On the right is a representation of a man-made, phospholipid bilayer liposome.

A liposome, while resembling a micelle, is different in that it is a sphere composed of one or more phospholipid bilayers. In order to arrange into a bilayer, we need energy in the form of heat, homogenization or ultrasonic waves, to be provided to the system.

“Liposomes are a bubble-like structure​​​​​​​ composed of molecules called phospholipids. In the outer shell​​​​​​​, the phospholipids’ water-loving heads face outside. In the inner shell, the heads face an aqueous core. The phospholipid tails are between these two layers. “

The liposome manufacturing process

As afore mentioned, a liposome is artificially created. A plant-based lecithin or chemically synthesized phospholipid is usually combined with water and the active ingredient (vitamin, mineral or phytoextract) in precise ratios. The mixture is then treated with an external form of energy. This results in the encapsulation of the active ingredient within liposomes. Hydrophilic (water-loving and fat-repelling) ingredients are encapsulated in the aqueous core. Lipophilic (fat-loving and water-repelling) ingredients are, on the other hand, encapsulated within the lipid bilayer of the liposome. The liposome and its encapsulated ingredients are themselves, fully water-soluble at this point (2,3).

The encapsulation of fat-soluble and water-soluble ingredients by a liposome

The absorption of liposomal supplements by the human body

The absorption of lipids and phospholipids by the small intestine is a well-studied process. Recent studies have shown that similar digestion and absorption of liposomes and the ingredients that they encapsulate, takes place (4,5). Phospholipids are mainly digested in the small intestine and not the stomach. Ingredients encapsulated in liposomes are therefore protected from gastric digestion. This results in their protection from a potential loss of activity. The gastric tract is also, in turn, protected from the potential inflammatory effects of the encapsulated ingredient.

The gastric stability and intestinal absorption of liposomes are highest at the nanoscopic level (>150nm). This is because the small size increases the retention time in the first part of the small intestine. This, in turn, allows for increased absorption and decreased excretion of the active ingredient.

Finally, the accompaniment of ingredients by lipid molecules can divert the uptake of at least a part of the ingredients. These ingredients are diverted towards the intestinal lymphatic system and not into the portal vein. This means that rather than passing through the liver, the ingredient directly reaches the bloodstream. Ingredients that pass through the liver are further digested, leading to a potential loss of ingredients. Reaching the bloodstream without passing the liver, therefore, increases their bioavailability.

Liposomes: Increasing the bioavailability of encapsulated ingredients

Bioavailability refers to the percentage of an ingredient that is available in the bloodstream after its administration. For example, if you eat 100 mg of vitamin C, the amount of vitamin C detectable in your blood will indicate its bioavailability. The closer the bioavailability of a certain ingredient is to 100%, the more profound or lasting will its effect be. This is because more of the ingredient will be able to reach its site of action, for example, your muscles.

Several studies have proven the increased bioavailability of active ingredients upon liposomal encapsulation (6,7,8). This includes water-soluble ingredients like Vitamin C but more importantly, fat-soluble ingredients like curcumin. We can attribute this increased bioavailability to the increased protection and absorption that liposomes provide.

Further, since liposomes are able to increase the bioavailability of the encapsulated ingredients, only a lower dose of the ingredient needs to be administered. This decreases the possible side effects of ingredient overdosing.

The human body’s liposomal excretion process

The phospholipids in the liposomes are likely excreted from the body through faeces or urine. Alternatively, they can be absorbed by various tissues for their metabolic potential.

You may have questions on whether taking liposomal supplements will cause you to put on weight because, in fact, they are made of fatty acids. However, studies so far, have shown no such effect of phospholipids. On the contrary, phospholipids have been shown to reduce the absorption of cholesterol, the molecule that makes you put on weight (9). While we do not claim that liposomes are a weight-loss remedy, we can assure you that we have not come across any studies linking an increase in body fat to liposome consumption.

Are there any safety concerns associated with the ingestion of liposomes?

There are no known safety concerns associated with the consumption of liposomal food supplements. Liposomes have been used as a drug delivery vehicle for more than two decades now. In this time, there have been no known side effects from the liposomes themselves. Doxil® was first approved in 1995 as liposomal doxorubicin for anti-cancer therapy (10). Since then, liposomes have shown promise as gene delivery systems for clinical gene therapy. They have also been especially beneficial for the delivery of poorly water-soluble substances. Ingredients such as curcumin, in the dietary supplement industry, greatly benefit from liposomal delivery (7).

Further, the use of naturally-derived phospholipids such as sunflower or soy lecithins in the manufacture of liposomes, makes them biocompatible and non-toxic (10). Liposomes also do not elicit an immune response when administered orally, intramuscularly or intravenously.

Liposomes are thus safe to consume.

Key takeaways:

• Liposomes are synthetic phospholipid bilayer nanospheres. Phospholipids composed of water-loving phospho heads and water-repelling lipid tails, make liposomes water-soluble.
• Liposomes are good vehicles for the transport of ingredients because they protect the encapsulated ingredients from gastric digestion, increase intestinal absorption and thus increase the ingredients’ bioavailability.
• Liposomes are biocompatible and non-toxic and are thus safe to consume.

References

1. https://courses.lumenlearning.com/boundless-biology/chapter/lipids/. Accessed on 26 October 2020.
2. Mozafari MR. Liposomes: An overview of manufacturing techniques. Cell. Mol. Bio. Letters (2005); 10: 711–719.
3. Patil YP & Jadhav S. Novel methods for liposome preparation. Chem. Phys. Lipids (2014); 177: 8–18.
4. Porter CJH, Trevaskis NL & Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nature Reviews: Drug discovery (2007); 6: 231- 248.
5. Liu W, Li D, Dong Z et al. Insight into the in vivo translocation of oral liposomes by fluorescence resonance energy transfer effect. Int. J. Pharmaceutics (2020); 587: 119682.
6. Davis JL, Paris HL, Beals JW et al. Liposomal-encapsulated Ascorbic Acid: Influence on Vitamin C Bioavailability and Capacity to Protect Against Ischemia-Reperfusion Injury. Nutrition and Metabolic Insights (2016);9: 25–30.
7. Prasad S, Tyagi AK & Aggarwal BB. Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: The Golden Pigment from Golden Spice. Cancer Research and Treatment (2014); 46(1).
8. Goktas Z, zu Y, Abbasi M et al. Recent advances in nano-encapsulation of phytochemicals to combat obesity and its comorbidities. J. Agric. Food Chem. (2020); 68 (31): 8119–8131.
9. Cohn JS, Kamili A, Wat E et al. Dietary Phospholipids and Intestinal Cholesterol Absorption. Nutrients (2010); 2(2): 116–127.
10. Zylberberg C & Matosevic S. Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape, Drug Delivery (2016); 23:9, 3319–3329.