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Liposomal technology and CBD

21/04/2020 7 MIN. READ Tim Dresemann
21/04/2020 7 MIN. READ Tim Dresemann

Cannabis is currently experiencing an unparalleled renaissance in medicine. And even if the traditional use in the form of flowers still has its place - due to scientific findings and modern technologies, the millennia-old medicinal plant is currently receiving one or two upgrades, especially with regard to its forms of application.

No matter what these developments are aimed at: Bioavailability, duration of action, time to onset of action, avoidance of undesired effects or safe and simple dosage - the goal is logically always optimization. Often, technologies are used that have long been part of the standard repertoire in the manufacture of other products. This also applies to so-called liposomal technology or "liposome-based technology".

Liposome technique: Why the effort?

But before we dive into this fascinating topic: Why even bother? What problems does the application of liposomal technology solve in relation to cannabis-based drugs?

One problem with conventional CBD use is the rather meager bioavailability. Bioavailability is a term from pharmacology and describes the proportion of an ingested substance or active ingredient that reaches the bloodstream unchanged and can thus reach its destination.

You only understand railroad station and would like to get into the topic earlier? No problem: What CBD is all about, you can read here for example. And in case you are wondering, no - CBD does not make you high! For the notorious intoxication another cannabinoid is responsible: THC. Find out more about this in our hemp-wiki article CBD vs. THC.

Poor bioavailability: What is the cause?

Due to the poor water solubility of CBD, it is assumed that it is absorbed from the gastrointestinal tract relatively slowly and irregularly. Thus, the "fate" or rather the dynamics of CBD in the organism (i.e. pharmacokinetics) is subject to strong fluctuations and therefore rather suboptimal in this context.

The bioavailability for CBD is estimated to be only 6% after oral administration according to the WHO. Although inhalation intake, i.e. by vaporization or smoking, is significantly more effective, smoking cannot be recommended under any circumstances from a medical point of view. Vaporization is also viewed critically by some medical professionals; the lung, so one argument, is there for breathing - not for taking medication (the asthmatic who wishes to protest at this point can be assured that he is the legitimate exception in this case).

In addition, on its way to the site of action (just like other cannabinoids) CBD first passes from the stomach to the liver, where it is extensively metabolized or "converted". In this context one speaks of the "first-pass effect". In fact, it is actually the case that - pharmacologically speaking - it is not the CBD that develops its effect in the organism, but 7-OH-CBD, a metabolite of the CBD.

The time until the onset of action is a further factor, the optimization of which occupies many researchers and also industry. In addition to the above-mentioned "first-pass effect", passage through the stomach and liver simply requires a certain amount of time. If the maximum effect after inhalation (i.e. vaporization or smoking) occurs after only a few minutes, it can take up to 90 minutes after oral absorption.

So there is still room for improvement in the optimization of cannabis-based drugs and their dosage forms. At first glance, however, there are limits to this because of the basic substance properties of cannabinoids such as CBD. They are not water soluble and that would be the end of this story. Actually! Because this is exactly where liposomal technology comes into play, or as it is called in technical jargon, "Liposomal Drug Delivery Systems".

What are liposomes?

Stellt sich also die Frage: Was sind Liposomen überhaupt und wie können sie dabei helfen, die eingangs beschriebenen Probleme – zumindest teilweise – zu beheben?

Vereinfacht kann man sich den Aufbau eines Liposoms wie ein (sehr kleines) Seifenbläschen vorstellen, das sich in einer wässrigen Lösung befindet. Im Innern dieses Bläschen befindet sich ebenfalls eine wässrige Phase. Die Hülle eines Liposoms besteht aus einer Doppelschicht von Phospholipiden.

Liposomale Technologie

Phospholipids have special biophysical properties: they consist of 2 parts - a water-loving (and fat-avoiding) "head" and a fat-loving (and water-avoiding) "tail". When several of these molecules are dispersed, i.e. distributed, in an aqueous medium, they form lamellar layers: The polar head group points into the aqueous area, while the fatty acid groups are opposite and point towards each other. This is how a spherical, bubble-like structure is formed - a liposome.

A liposome is thus basically an aqueous compartment surrounded by a bilayer (a membrane) consisting of (at least) 2 layers of phospholipids.

By the way: If you now think that this sounds somehow familiar to you, you are probably right, because phospholipids are a popular topic in bio-lessons as the main component of biomembranes.

Advantages of the liposomal formulation

Well, but how exactly do manufacturers of vitamins, dietary supplements, pharmaceuticals and of course CBD take advantage of the special properties of liposomes?

In the liposomal formulation of drugs (and also of e.g. vitamin C, etc.) the substances concerned are either placed inside the liposome, i.e. in the aqueous compartment (applies to water-soluble substances), or in the membrane itself (applies to fat-soluble substances, such as cannabinoids).

Let us remember: Cannabinoids, including CBD and THC, are difficult to dissolve in water, but are fat-soluble. In liposomal formulations, this group of substances is thus enclosed inside the double lipid membrane and thus protected from unwanted metabolism. On the one hand, the plasma half-life of a drug can be extended by protecting the liposome, i.e. the time that this substance remains in the patient's blood plasma and can thus also develop its effect.

The liposomes loaded with CBD are transported to the site of action after ingestion (e.g. in the form of capsules or as drops). Here the double lipid layer of the liposomes fuses with the membrane of the receiving cell. In this way, the charge is quasi transported into the cell interior. The liposomal release of the active ingredient takes place in 4 steps:

Step 1

Docking (adsorption) of the liposome to the cell membrane

Step 2

The internalization ("swallowing") of the liposome by the cell by invagination of the cell membrane (= endocytosis)

Step 3

The fusion of liposome and cell membrane and thus release of liposomal content into the cytoplasm, i.e. into the interior of the cell

Step 4

Lipid Exchange

Excursus: lipid exchange

In short, if a defined quantity of certain substances, including CBDs, is administered as a liposomal formulation, it can be assumed that the effect is much more efficient than if the same quantity of the substance had been administered "conventionally", i.e. without using liposomal technology. Efficiency and therapeutic breadth of the active substances are increased.

But beware: Even if you stumble upon such statements on the Internet again and again - the fact that you can formulate CBD in this way does not mean that the result is a water-soluble CBD!

Water-soluble CBD does not exist. Liposomally formulated CBD could at best be described as "water-compatible". But even with this, a lot has already been gained.

Liposomal formulation of cannabinoids

For this purpose, an emulsion is first produced from phospholipids and water. Now energy is added, e.g. in the form of ultrasound, as mechanical energy (shaking) or heat. In order to achieve a thermodynamic equilibrium, spherical vesicles - liposomes - are formed, which are surrounded by a double membrane.

Depending on size, number of membrane layers, composition and manufacturing methods there are different classes of liposomes, which are named accordingly, e.g. LUV's and SUV's ("Large" or "Small Unilamellar Vesicles").

Challenges in the production of liposomal CBD formulations

A critical property of liposomes is their stability. A good stability of several months up to several years is mandatory for the trade.

The problem: over time the small vesicles tend to fuse together and thus increase in size. The stored substances can also escape from the vesicles, which can promote the above-mentioned fusion to larger structures, or lead to the destruction of the vesicle. These processes can be counteracted by specially developed steps in the manufacturing process. Right at the beginning of the manufacturing process, the size distribution of the individual vesicles and their morphology, which should be as uniform as possible, is crucial.

An important factor is the use of suitable phospholipids as starting material. The hydrophobic "tail" of a phospholipid can consist of saturated, unsaturated or a combination of saturated and unsaturated fatty acids. The exact composition determines the fluidity of the resulting membrane and thus the stability of the liposome. The use of suitable, high-quality and as fresh as possible reagents is therefore crucial.

Other chemical and physical factors such as pH, temperature, exposure to light and the presence of oxygen also play a role in the production process. Finally, sterilization is also a challenge: high temperatures or irradiation would normally be used here.

However, liposomes react very sensitively to both and make other methods necessary. For example, membrane filters (22µm) can be used, or the entire production can be carried out under aseptic conditions.

Sounds complicated. Is it still worth it?

All this does not make the manufacturing process any easier and it requires a great deal of know-how and experience to fine-tune all sub-processes so that the result is a functional, efficient, stable and above all safe product.

That - and nothing less - is our claim at VAAY. What else you can expect from our products, you can read in our quality promise.

The increased technical effort in production is accordingly reflected in the production costs and ultimately in the product price. A certain amount of CBD, produced with liposomal technology, will generally be more expensive than the same amount of CBD offered as conventional extract in capsules.

However, increased bioavailability through liposomal formulation can cause the liposomally ingested CBD to unfold its effects more efficiently, leading to a better CBD experience for the user.


Cannabis as a medicine is moving back into the focus of modern research after decades of prohibitionist policies. Even if the fields of application today largely coincide with those historically handed down - in terms of dosage form, bioavailability (efficiency), speed of action and safety, a tremendous development has taken place during this time. So perhaps it is time that cannabis also gets an upgrade in these areas.

The challenges that cannabinoids pose as active ingredients are not new: many vitamins and nutrients, such as vitamin C or curcumin, the value-giving ingredient of turmeric, also have low bioavailability and are therefore increasingly offered as liposomal formulations.

The technology is therefore known, tested and can actually be applied to cannabinoids. The advantages in terms of pharmacodynamics and pharmacokinetics are numerous. Liposomal technology does not magically make CBD water-soluble - but it is "water-compatible".

Cannabis-based drugs and cannabinoids in general have thus arrived in the 21st century, so to speak, and, through the use of modern pharmaceutical technology, are on their way to securing a permanent place in our everyday lives, among other things as optimized and high-performance formulations. Just like curcumin or vitamin C.

Do you want to learn more about cannabis or hemp? Click here to go to our hemp wiki.

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