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Vitamin C

Liposomal delivery of Vitamin C: benefits of the envelopes and ZIP-codes

When you send a letter – you do not just throw it as it is in a mailbox, do you?

You carefully fold your letter, put it in an envelope and seal it. You write a destination address and put a stamp. You make sure, that your letter is delivered safe, sound and on time. If the recipient gets only a piece of the letter – you will not be satisfied with the delivery, right?

That is why you put your letter in the envelope.

Did you know that the same principles could be applied to deliveries happening inside our bodies?

Oxygen does not just “float” in the blood – it is bound to hemoglobin inside red blood cells

Proteins, synthesized by our cells, have specific localization signals: those that must stay inside are never secreted to the outside and the other way around

Lipids, up-taken by our intestines from food, are transported as chylomicrons, not single molecules

Our body knows how to use envelopes!

Surely, it was only a matter of time, until pharmaceutical industry develops its own envelopes. Many different options for targeted supplement and drug delivery were invented by now, but today we will discuss Liposomes and their application for delivering food supplements, such as Vitamin C.

Membrane – a border checkpoint of every cell

Our body is an extremely complex system, constantly struggling to maintain order within itself. Every piece should be exactly where it is expected to be and not somewhere else. It is not surprising, that molecules do not freely travel around, but being specifically transported.

Otherwise we would not be human beings, but a soup!

One fundamental biological invention, that prevents us from being a soup, is a cell. Our entire body is composed of cells – “the functional basic units of life”. The word “cell” comes from Latin “cella”, which means “a small room”.

If we imagine a cell as a small room, then the cell membrane would be its wall. All sorts of things cover this wall: direction signs, air conditioners, antennas and cameras. But most importantly – there are various doors of any sizes and shapes imaginable.

Those doors are the channels and their job is to decide, who is allowed to come in or exit the room

That is what a channel looks like: an entry point for the molecules

Channels are of utmost importance to the cell for two reasons:

  1. Selectivity: different molecules need different channels to go through the membrane
    • Some channels can let a group of similar molecules pass, while others let only one type of molecule
    • Some channels only let molecules in, while others – only let them out
  2. Regulation: activity of the channels is tightly regulated by the cell
    • Channels can be opened and closed, depending on the needs of the cell and signals that the cell receives – it is as easy as locking or unlocking a door
    • A cell can decide, which types of channels to put on its membrane and how many channels of each type it needs

Together those two properties of channels allow a cell to regulate the abundancy of each molecule inside it individually.

Restricted area: authorized molecules only!
The tightest control in terms of molecular transport takes place in our brain. Neurons never uptake nutrients directly from the blood, as other cells do. Blood vessels in the brain are surrounded by special cells – astrocytes. Their main job is to decide, which molecules are allowed to pass and which are not. This system is called BBB – Blood-Brain Barrier. Blood-Brain Barrier not only filters molecules but also does not let pathogens enter our brain. That is why brain infections are so rare and only specially adapted pathogens can cause them. On the other hand, BBB has its drawbacks. It limits Immune System components entry to the brain, so we cannot fully protect ourselves in case the infection did occur there. In addition, BBB complicates the treatment of brain diseases, since not all drugs are able to pass either. Still, BBB is of utmost importance to our brain homeostasis. Disruptions in BBB contributes to various diseases, such as multiple sclerosis, Alzheimer’s and others1,2

But there is more to it!

As there is a variety of channels and molecules, different molecules are transported in different fashion.

Let’s look at these “fashions” more closely and take Vitamin C as an example

  1. Diffusion through the membrane

Some molecules are like ghosts – they can go through the walls without any doors!

Concentration gradient If the concentration of a “ghost” molecule is higher outside the cell than inside – the molecule enters If the concentration inside the cell is higher than outside – the molecule exits

They do not need a channel or energy to enter the cell. The only condition is the presence of concentration gradient.

As tempting as it might seem, this type of transportation has two major drawback:

  • It cannot be regulated, as it does not involve a channel
  • It is very slow

Therefore, there are not so many “ghost” molecules. Among them are steroid hormones and small gases (CO2, N2, O2)3

What about Vitamin C?

Unfortunately, Vitamin C is really bad at being the “ghost” molecule

2. Facilitated diffusion

As it was mentioned, diffusion through cell membrane is a slow and poorly regulated process

However, nature is smart – it has invented channels to make things better!

Channels for facilitated diffusion are open doors for molecules. The principle of cell entry is the same as in diffusion through the membrane: it is dependent on concentration gradient and does not require energy. However, going through the channel is much easier, that squeezing through the membrane. Also, due to the properties of the channels described above, this process can be regulated by the cell.

What about Vitamin C?

Only oxidized form of Vitamin C (DHAA – dehydro-L-ascorbic acid) is uptaken by the cells of our intestine by facilitated diffusion4,5

3. Active transport

What does a cell do, if the diffusion is too slow or concentration gradient is not present?

It resorts to active transport!

Active transport is performed by special protein transporters. They work like channels, only they are paid better! To transport a molecule through protein transporter a cell should spend some energy currency.

Generally the fee is paid in two steps:

  1. First, primary active transporters spend energy to transport ions against the concentration gradient: for example, export sodium and import potassium
  2. Second, these ions go through another transporter in a Facilitated diffusion-like manner (following the concentration gradient – so in reverse direction) and that ion movement enables this transporter to transport another molecule
    • If both ion and transported molecule go in – it is a symport
    • If ion goes out and transported molecule goes in – it is an antiport

What about Vitamin C?

Vitamin C in a form of ascorbate is actively transported to the cell together with sodium ions (symport) 4,5


The amount of Vitamin C absorbed in the intestines in a period of time is quite limited

  • Diffusion is not possible, facilitated diffusion is slow and limited by a concentration gradient.
  • Active transport is limited by the amount of energy the cell has. Vitamin C – is only one of many other molecules that are being actively transported
Vitamin C is taken into the cell -> its concentration in the cell grows -> the difference between concentrations of Vitamin C inside and outside the cell drops down -> uptake by facilitated diffusion slows down and finally stops

What if we need more Vitamin C – how can we overcome these limits?

The answer is – we need to stop relying on channels and give Vitamin C a ghost-like properties!

But how is It done?

To be or not to be – dissolved?

Why Vitamin C is not a “ghost” molecule in the first place? Why can’t it just go through the membrane?

To understand that we need to take a closer look on the membrane itself.

The cell membrane is built of special lipids. Those lipids have two components:

  • “Head” – a polar part
  • “Tails” – a non-polar part
The architecture of a typical membrane lipid
If we talk about the type of charge, then works the rule “opposites attract”: (+) is attracted to (-) and (-) to (+) If we talk about the presence of a charge, then works the rule “similarities attract”: polar molecules are attracted to polar molecules and non-polar molecules are attracted to non-polar molecules

Why is that important?

As we know, our body is mostly composed of water. Water molecules are polar: they are dipoles, which means, that every water molecule has a (+) charged pole and a (–) charged pole – just like a magnet. Other polar molecules easily interact with water: their (+) pole interacts with the (-) pole of a water molecule and the other way around. This is what makes polar molecules water-soluble. Charged molecules have only one “pole”, but they interact just the same.

Such molecules are called “hydrophilic”

On the other hand, molecules without a charge cannot really interact with water, which makes them insoluble in water. Such molecules can only be dissolved by non-polar dissolvent, such as petrol or kerosene. If you still attempt to dissolve them in polar dissolvent – they will stick to each other, forming small non-polar microenvironments. You can observe that phenomenon, if you add a bit of oil to water: oil will form drops (microenvironments), but will not be dissolved.

Mix the unmixable
There are special molecules that one can add to a solution in order to overcome that discrepancy in polarity. Those molecules are called “emulsifiers” and are widely applied in the food industry. The most common emulsifier that can be found in every kitchen is a chicken egg. Thanks to the emulsifier properties of an egg we can mix water and butter into doe – and even mix it with air while whipping

Such molecules are called “hydrophobic”

But what are lipids then?

Lipids are amphiphilic: which means, that they have both hydrophilic and hydrophobic parts.

Heads of lipids easily interact with water, while tails do not

Cell membrane is a border between water solution inside the cell (cytoplasm) and water solution outside the cell (extracellular space). In such conditions, lipids of the membrane form a bilayer:

  • Hydrophilic heads of the inner lipid layer face the cytoplasm
  • Hydrophilic heads of the outer lipid layer face the extracellular space
  • Hydrophobic tails of both layers face each other, thus forming a hydrophobic layer (microenvironment) in between two layers of hydrophilic heads

That is how the membrane is built

The membrane is basically a sandwitch
Important: there are different sorts of lipids. Not all lipids are amphiphilic. Not all amphiphilic lipids are suitable for forming membranes.

So why Vitamin C cannot diffuse through the membrane?

In our bodies, Vitamin C is charged, which means, that it is hydrophilic. As with other hydrophilic molecules, that Vitamin C is unable to squeeze through the membrane due to its hydrophobic layer. Vitamin C cannot interact with tails of membrane lipids, so it cannot be a “ghost”.

Well, at least without an envelope!

Liposomes – magical envelopes for Vitamin C

What makes liposomes so magical?

Liposomes are made of the same lipid bilayer, as membranes of our own cells!

The major difference is in size: while cell membrane surrounds a huge machinery of the entire cell, liposomal membrane forms a tiny little bubble. However, this bubble is big enough for us to put something inside it.

How about we put there Vitamin C?

Liposome with Vitamin C

The point is, that when a liposomal membrane makes a contact with the membrane of the cell, the lipids of the membranes start to interact – heads with heads, tail with tails. It causes lipid rearrangements. As a result, liposomal and cellular membranes fuse together – just like two bubbles. And the insides of the liposome end up inside the cell!

Is not that magical?

There are two main benefits in delivery using Liposomal envelopes:

  1. Independency: fusion of the membranes does not require energy, special transporter or channel proteins and Vitamin C concentration gradient also does not play a role
  2. Concentration: one fusion transports many molecules inside the cell at once, while transport via a channel or a transporter transfers molecules one by one
Delivery of Vitamin C: through a channel or using a liposome. Compare the magnitude!

In 2016 Janelle L. Davis has published a study about Vitamin C delivery. In the study three methods of Vitamin C administration were compared: oral liposomal, oral non-liposomal, and intravenous injection. 11 adults got either 4g of Vitamin C or placebo by one of the described above methods. 1,2 3, and 4 hours after administration blood samples were taken from the patients, and concentration of Vitamin C in plasma was measured6.

Concentration of Vitamin C in blood was higher after consuming Liposome-encapsulated vitamin compared to non-encapsulated

Graphs from the study6, showing the concentrations of Vitamin C in plasma. A – all methods of administration together, B – the same results, but without intravenous method

Liposomal technology is a growing field. In clinic, liposomes are used for drug delivery during treatment of various diseases, including cancer7. Liposomal technology is constantly being developed, new ways of creating Liposomes are invented and tested for Vitamin C8, Vitamin E9 and other supplements and drugs. A variety of supplements in liposomal form have gone through the trials and tests and now available on the market: different vitamins, glutathione, magnesium and many others.


  1. Our body tightly regulates the transportation of molecules – it is necessary to prevent diseases
  2. A great contribution to this regulation makes a cell membrane. Without it everything would mix and we would become a soup
  3. Transport through the cell membrane can follow three mechanisms: direct diffusion through the membrane facilitated diffusion through the channel, and active transport through the transporter
  4. The membrane itself is built of lipids, which form a bilayer: hydrophilic lipid heads face cytoplasm and extracellular space, while their tails face each other, forming a hydrophobic layer inside the membrane
  5. Vitamin C is capable of facilitated diffusion and active transport, but its uptake by intestinal cells is limited by the concentration gradient and energy stock
  6. Vitamin C is charged and thus hydrophilic. It means, that Vitamin C cannot go into the cell by direct diffusion, because of incapability to interact with the hydrophobic layer of the membrane.
  7. Liposomes are small spheres. One can put various molecules inside them, including Vitamin C
  8. The wall of a liposome is formed by a lipid bilayer (just like a cell membrane).
  9. When liposomal wall touches the cell membrane, lipids interact and the membranes fuse, and thus the insides of a liposome end up inside the cell
  10. It was shown, that liposomal Vitamin C reaches the blood in higher abundancy, compared to non-liposomal
  11. Liposomal technology is constantly being developed. It is used not only for food supplements but also in therapy for drug delivery


  1. Waubant E. Biomarkers indicative of blood-brain barrier disruption in multiple sclerosis. Dis Markers. 2006;22(4):235-244. doi:10.1155/2006/709869
  2. Ujiie M, Dickstein DL, Carlow DA, Jefferies WA. Blood-brain barrier permeability precedes senile plaque formation in an Alzheimer disease model. Microcirculation. 2003;10(6):463-470. doi:10.1038/
  3. Oren I, Fleishman SJ, Kessel A, Ben-Tal N. Free diffusion of steroid hormones across biomembranes: a simplex search with implicit solvent model calculations. Biophys J. 2004;87(2):768-779. doi:10.1529/biophysj.103.035527
  4. Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011;437(3):357-372. doi:10.1042/BJ20110326
  5. Wilson JX. Regulation of vitamin C transport. Annu Rev Nutr. 2005;25:105-125. doi:10.1146/annurev.nutr.25.050304.092647
  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. Nutr Metab Insights. 2016;9:25-30. Published 2016 Jun 20. doi:10.4137/NMI.S39764
  7. Kraft JC, Freeling JP, Wang Z, Ho RJ. Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems. J Pharm Sci. 2014;103(1):29-52. doi:10.1002/jps.23773
  8. Łukawski M, Dałek P, Borowik T, et al. New oral liposomal vitamin C formulation: properties and bioavailability. J Liposome Res. 2020;30(3):227-234. doi:10.1080/08982104.2019.1630642
  9. Padamwar MN, Pokharkar VB. Development of vitamin loaded topical liposomal formulation using factorial design approach: drug deposition and stability. Int J Pharm. 2006;320(1-2):37-44. doi:10.1016/j.ijpharm.2006.04.001
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