Superfine Particle Nanocapsule Technology

Particularly effective for materials such as macromolecule polysaccharides like Fucoidan and Fucoxanthin, which break down easily

Ten times the absorbability, and 17 times the absorption (efficiency in the body)! Nanocapsule Technology

What are Nanocapsules?

Nanocapsules are a special technology, born from the latest nanotechnology, which are made up of extremely small capsule shapes that are so tiny they look like granules.
They are made of artificial membrane whose main ingredient is phospholipid.

The inside of the microparticles make use of latest research in the field of chemical carriers (substances used to transfer materials) in order to encapsulate hydrophilic constituents (water-soluble materials) and lipophilic ingredients (fat-soluble materials), and also in the field of absorption enhancers.

The nanocapsules available from this website were developed to utilize this technology in the field of functional foods. Effects that can be expected from ingesting the functional ingredients enclosed in nanocapsule microparticles are a substantial improvement of the absorption rates of the ingredients, protection of the compound from breakdown due to attack from digestive enzymes in the stomach and intestines, and improved taste (the taste elements are protected so that there is no unpleasant taste).

[Diagram 1] Conceptual image of size and shape of Nanocapsules

What are Nanocapsules?

Image of Vital Nucleic Acid Fucoidan Nano Premium using our company's nanocapsule technology

Properties of highly functional health food nanocapsules

Unlike regular products that use chemicals, they are manufactured using methods that use only food ingredients.

Technologies using liposomes have only been utilized in specific chemical-related fields up until now, so manufacturing processes using high-priced ingredients have been the mainstream.
It has been very difficult to use the Nanocapsule size preparations for food ingredients only, and because of this it was not possible to use them for products that could be ingested by humans safely and with peace of mind over the long term, so up until now they were thought to be difficult to apply to the field of foods.

Due to the development of our proprietary products, and the new development of our new proprietary processing technology for nanocapsules for food use, we have made possible nanocapsules that use only food ingredients.

[Photo 1 and Photo 2]

Characteristics of Nanocapsule Technology

Protection from stomach acid and pancreatic fluid can be expected. [Diagram 3]

All compounds ingested by mouth are broken down by digestive enzymes, starting with saliva and after that stomach acids, pancreatic fluid and bile etc. These are bodily functions essential to human beings for ingesting nutrients and supporting life's activities, but sometimes they have harmful effects. For example, there is great benefit in protecting ingredients with structures that break down easily, such as Fucoxanthin (the pigment in Fucoidan, thought to be closely involved in apoptosis, a critical characteristic of Fucoidan), from attack by digestive enzymes. Nanocapsules increase the bioavailability of these kinds of ingredients by protecting them from stomach acid and pancreatic fluid.

[Diagram 3]

Improved absorbability can be anticipated. [Diagram 4]

We prepared the diameter of a Nanocapsule particle at the 100-500nm required for intestinal absorption, so improvement of the intestinal absorption rate of the functional ingredients can be expected.

[Diagram 4]

Nanocapsule Safety

We are carrying out a variety of tests in order to deliver complete safety.
Safety of the nanocapsules was confirmed by single-dose toxicity tests using mice.
We monitored the controls (the group of mice who had not received anything) with the group who had taken the nanocapsules under the same conditions many times, over time.
The results confirmed that no abnormalities whatsoever were observed in the group that had taken the nanocapsules, and that nanocapsules are safe.

Evaluation of nanocapsules in protection from stomach acid and pancreative fluid etc.

Testing of curcumin in autumn turmeric extract encapsulated in nanocapsules, using stomach acid test and pancreatic fluid test (in vitro study level).

Autumn turmeric, which has recently attracted attention as an Okinawan health ingredient and has become well known to the general public as well, contains a variety of compounds.
Among them, curcumin in particular has attracted a great deal of attention, and many companies are using it in their products.

However, curcumin when ingested is broken down by the harsh environments of stomach acid and intestinal fluids, and it can be predicted that the amount of ingredients that reach the intestines is much smaller than the amount prior to ingestion. 
Here, using autumn turmeric extract and autumn turmeric extract encapsulated in nanocapsules, we processed at the in vitro level artificial stomach acid (pH2.0, pepsin) and artificial pancreatic fluid (pH8.3, pancreatin), and verified that in the autumn turmeric extract encapsulated in nanocapsules, the functional ingredient curcumin was protected from digestive fluids.

[Diagram 4] Total curcumin survival rate in the stomach acid processing test and pancreatic fluid processing test

Results of stomach acid and pancreatic fluid processing tests confirmed that the curcumin in regular autumn turmeric extract was easily affected by pancreatic fluid in particular, and only 46.6% survived, but the curcumin in autumn turmeric extract encapsulated in nanocapsules was protected from assaults by stomach acid and pancreatic fluid, and 90.3% survived.

Testing of absorbability when curcumin is enclosed in nanocapsules, using blood curcumin kinetics

The problem is that it is difficult to obtain the expected effect from a small dose, because curcumin, the functional ingredient in autumn turmeric, cannot be dissolved in water because it is a lipophilic (fat-soluble) ingredient, in addition the curcumins aggregate together in water, so it is extremely poorly absorbed through the intestines.

Here, we measured the blood curcumin concentration in rats given oral dosages of curcumin in a normal state and with curcumin encapsulated in nanocapsules, and verified that absorption was improved with encapsulated curcumin.

We collected blood samples 30, 60 and 120 minutes after dosing, prepared blood serum from the blood obtained, sampled the curcumin at multiple stages, and measured and made calculations of the curcumin concentrations.

The results showed that compared to the blood curcumin concentrations of the group who were administered curcumin only, the blood curcumin concentration of the group who were administered curcumin encapsulated in nanocapsules were 5-10 times higher, and there was a significant difference (P < 0.01) at 30-120 minutes.

[Diagram 5]

[Diagram 5]
From the above results, we believe that encapsulating curcumin in nanocapsules protects curcumin from the harsh environments of stomach acid and intestinal fluids, and by enhancing the absorption rate even more, it will be possible to increase the blood curcumin concentration even more.

Therefore, higher functionality can be expected from curcumin encapsulated in nanocapsules than from regular curcumin. Also, autumn turmeric contains various functional food ingredients other than curcumin, such as curcumin derivatives, so these results using autumn turmeric encapsulated in nanocapsules suggest that by increasing the absorption rate of compounds other than curcumin in the same way, it will be easy to obtain their expected characteristics.

Predicted intestinal absorption when Fucoidan is encapsulated in nanocapsules

(Small intestine model test using intestine-derived Caco-2 cells)

Fucoidan that is extracted from Okinawan mozuku is a type of soluble dietary fiber. It is an indigestible substance that is not broken down inside the human body by degrading enzymes, and it was considered to be difficult to absorb through the intestines.

Also, Fucoidan is a macromolecule polysaccharide. Naturally, because it is poorly absorbed through the intestines, it was difficult to obtain the expected properties from small doses.

In the past, some researchers tried to improve absorption by breaking down the molecular weight of Fucoidan itself and giving it a low molecular weight (a molecular weight of about 500), but this method took away the properties of Fucoidan itself, which is a macromolecule, and as a result even though absorption was improved, the method was useless for enhancing the desired properties.

That is why we experimented with nanocapsules as a technology for improving absorption while keeping the Fucoidan macromolecules.

We created a small intestine model using Caco-2 cells derived from the human digestive system, and evaluated the absorption of regular Fucoidan and Fucoidan encapsulated in nanocapsules, and measured the difference in absorption rate.
This is a generic method for tests measuring drug permeability.

[Diagram 10]

We added a 1.0% solution of each specimen to the upper layer membrane of monolayer Caco-2 cells on the intestine (Apical) side, and after culturing for 2 hours, evaluated the amount of Fucoidan that had permeated into the lower layer of the monolayer membrane on the basement membrane (Basal) side by measuring the amount of fucose.

Results of the difference in absorption between the Fucoidan in regular format and Fucoidan encapsulated in nanocapsules

The results confirmed that both samples: Fucoidan and Fucoidan enclosed in nanocapsules, permeated the small intestine model.

Furthermore, the difference was clearly shown in the amount of permeation of 4.84 (μg/cm2/h) of the Fucoidan encapsulated in nanocapsules versus 0.74 for the regular format Fucoidan.

[Diagram 11]

The permeation rate from the intestine side to the basement membrane side for the Fucoidan derived from Okinawan mozuku was 0.09%, and for the Fucoidan encapsulated in nanocapsules it was 1.51%, demonstrating around a 17-fold increase in permeation rate.

[Diagram 12]

Therefore, it was confirmed that encapsulation of Fucoidan in nanocapsules increases the amount of Fucoidan that permeates Caco-2 monolayer membrane. This demonstrates that Fucoidan encapsulated in nanocapsules absorbs more easily in the small intestine compared to regular Fucoidan.
Therefore, higher functionality can be expected from Fucoidan encapsulated in nanocapsules than from regular Fucoidan.

Nanocapsule technology optimal for poorly-absorbed substances or ones that are susceptible to attacks from digestive enzymes

Nanocapsule technology is the latest nanotechnology, and has achieved results that would have been considered impossible up until very recently.

In future it will be possible to deliver even better products by using nanocapsulization for a variety of substances.