INNOVATIONS

Nanovesicles are smart, food-grade nanocarriers engineered to tune the performance of the functional ingredients, both before consumption (i.e., production and shelf-life) and after consumption (i.e., in the digestive tract). Nulixir’s smart nanocarriers can easily incorporate any functional ingredient (e.g., hydrophobic or hydrophilic) into food and beverage products. Our library of ingredients includes tens of functional ingredients, such as cannabis derivatives, nootropics, vitamins, minerals, stimulants, adaptogens, and probiotics.

The majority of functional ingredients have undesirable taste, low bioavailability, slow onset, or release too quickly in the body. But, with Nulixir’s game-changing technology, you are no longer reduced to such compromises.

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Controlled-Kinetics and/or Organ-Targeted Release

The human body is sophisticated and rightly deserves sophisticated nutrition! Engineered release profiles enabled by nanovesicles provide a continuous, steady supply of desired nutrients, as opposed to a quick spike followed by a sharp drop of nutrient concentration in the bloodstream.

Nanovesicles offer tunable release kinetics, including extended-release, delayed-release, and stage-wise release, for the hosted functional ingredients. Controlled release kinetics can be tailored to products such as stimulants (e.g., caffeine), nootropics, and cannabis derivatives (e.g., CBD, CBN, Delta-8) for sustained release profiles to properly feed the body.
The protein industry, particularly in product segments targeted toward fitness and athletics, can also enjoy benefits related to sustained protein release, since a continuous uptake of protein is important for the development of muscle and throughout the recovery process.

Sleeping aid supplements are another vertical that benefit from extended releases. For example, melatonin, which is the human body’s natural compound for inducing sleepiness, can help consumers fall asleep when used as a supplement. However, a longstanding issue with such sleeping supplements is the rapid kinetics of release. For individuals with fast metabolism, their body will tend to process the melatonin quickly. This makes the supplement fast-acting but also fast to wear off, which may cause the consumer to wake up after a few hours. Extended and sustained release of sleeping aid supplements can induce uninterrupted sleep cycles of 6-8 hours.

By configuring the release and absorption properties of compounds, the potential side effects may be avoided and/or their severity reduced. Whether a product desires a quick release and sudden effect, or a slower and more sustained release, Nulixir’s specialized formulation can meet the needs of diverse markets. Such tailored release profiles are realized by the nanovesicle’s unique, customizable structure which allows for single- and multi-layer structures. Various functional ingredients can be incorporated into the different layers of these smart nanocarriers, enabling unlimited possibilities for release profiles and applications. The difference between a positive effect and a negative one is often attributed to correct dosage and release. With the ability to control this, our nanovesicle technology platform provides an ideal solution to a prevalent problem.

Nanovesicles can further control where the encapsulated functional ingredients will be released in the digestive tract. Organ-specific targeted release can boost the functionality and prevent structural damage in the harsh medium of the digestive tract.
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High bioavailability

Bioavailability refers to the percentage of consumed ingredients that are absorbed by our body and is of critical importance when quantifying health related benefits. While hydrophilic (water-soluble) ingredients typically possess high bioavailability, the same cannot be said of their hydrophobic (fat-soluble) counterparts. To enter the bloodstream, ingredients are required to permeate the membrane of the small intestine—this very process is an impediment to fat-soluble ingredients because the large structure of these ingredients is not well suited for passage through the fine pores of the membrane.
Cannabidiol (CBD), for example, has very limited bioavailability (~10%) and very slow onset (~15-25 minutes). Nulixir’s proprietary CBD nanovesicles can significantly increase the bioavailability (up to 10x) and provide extremely quick onsets (less than 1 minute).

Our nanovesicles are masterfully engineered with the right size and right surface chemistry, to ensure the vast majority of functional ingredients are quickly and efficiently absorbed by the bloodstream, thus providing superior onsets. The nanovesicles require no further processing by the digestive tract to facilitate the absorption; these smart nanocarriers can be readily absorbed and transferred to the bloodstream upon consumption.

High bioavailability results in less input ingredient (i.e., less cost) needed to achieve the same effect; therefore, by efficiently using functional ingredients, food and beverage manufacturers can reduce their COGS! This is made possible by our nanovesicle technology which protects functional ingredients from premature degradation and interaction with the physiological environment (before consumption), increases intracellular penetration, and enhances absorption kinetics dramatically (e.g., up to 10x enhanced bioavailability).

Mask undesired flavors

The addition of functional ingredients often introduces stray notes that result in unpleasant flavors. A common solution is to add a flavor masking agent to the formulation to offset the taste; however, this approach is often less than desirable. Commonly used flavor masking agents have an unpleasant aftertaste and simply fail to effectively mask strong tastes and aromas associated with products such as cannabinoids (strong taste of terpenes), protein supplements (the famous chalky flavor), energy stimulants (bitter taste), and nootropics (strong earthy notes). Nanovesicles, however, can effectively mask flavor by inhibiting direct interaction of the functional ingredients with the taste buds after consumption.
A key challenge for ready-to-drink beverages and shots is developing healthy, effective product formulations that are palatable. Consumers often complain about the bad taste of these products, especially in smaller formats (e.g., 1-2 oz shots). In response to this, producers resort to using a bevy of flavor additives and artificial sweeteners. Sometimes multiple additives are used to mask and balance the different flavors, resulting in an awkward flavor profile. Worse still, some of these flavors and artificial sweeteners can cause bloating and digestive problems in a percentage of consumers. Adding sugar to offset bitterness, as an example, may not always be an option, particularly for diet products. In contrast, our proprietary nanovesicles mask flavor without introducing compounds that may require masking and/or balancing themselves, or that may lead to digestive difficulties.

Increased shelf-life

Shelf-life is a function of the degradation mechanism of a specific product and can be influenced by factors such as exposure to light, heat, moisture, and contamination by micro-organisms. Bacterial contaminants are omnipresent, and foods left unused for long periods of time may be contaminated by bacterial colonies and become dangerous to eat. Shelf-life is not significantly studied during product development as manufacturers have economic and liability incentives to specify shorter shelf lives, encouraging consumers to discard and repurchase products.
Demand for functional ingredients with short shelf-life (e.g., probiotics) has steadily increased in light of several health benefit claims. Both shelf stable and refrigerated probiotics are readily available in grocery stores and health food stores. For beverages, the form of the probiotic strain is dependent on the finished product type and distribution channel. For example, live and active cultures are generally used in refrigerated products such as drinkable yogurt, kefir and kombucha, while the more robust spore form of microorganisms are often used in non-refrigerated beverages. The biggest issue is that they are not truly shelf-stable ready-to-drink (RTD) beverages. The organisms do not survive higher thermal processing conditions required to be used as an RTD additive.

Nulixir’s technology can improve shelf-life and guarantee a higher bacteria count over a longer period of time. Whether applied to probiotics, nootropics, vitamins and minerals, or energy stimulants, the nanovesicle technology can prolong the shelf-life of products by providing a proper sealing around these sensitive functional ingredients, thereby preventing direct interaction between the ingredients and the surrounding medium.

Nanovesicles: Customizable Nanocarriers

The structure and composition of nanovesicles can be tuned, through multiple operational knobs during manufacturing, to provide the desired functionality and properties.

With conventional nanotechnology alternatives such as nanoemulsions, micelles, and liposomes having been around for a considerable time, the need for robust nanocarriers in food and beverages is as compelling as ever. Nulixir’s nanovesicles exhibit considerable advantages over competing technologies.

Nanovesicles: Customizable Nanocarriers

Nanoemulsions are bi-continuous systems that are essentially composed of bulk phases of water and oil separated by an emulsifier region. Therefore, nanoemulsions are limited to only hydrophobic components (e.g., fat-soluble vitamins, CBD, or fish oil). The oil-based ingredients are blended with emulsifiers (e.g., surfactants) under high-pressure emulsifiers to stabilize the droplets. Although nanoemulsions are easier for the body to absorb compared to the oil itself, this technology is not without its downsides. In order to stabilize such dispersions, large amounts of surfactants are used, the majority of which are harsh chemicals commonly used in cosmetics. The nanoemulsions are thermodynamically unstable and kinetically stable liquid systems which means the stability may be lost upon changing the properties of the surrounding medium (e.g., pH, temperature, presence of other ingredients, etc.). The droplets are also prone to interacting with other compounds in the solution and coalescing to the walls of the container over time.

With conventional nanotechnology alternatives such as nanoemulsions, micelles, and liposomes having been around for a considerable time, the need for robust nanocarriers in food and beverages is as compelling as ever. Nulixir’s nanovesicles exhibit considerable advantages over competing technologies.
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Nanovesicles vs. Nanoemulsions

Nanoemulsions are bi-continuous systems that are essentially composed of bulk phases of water and oil separated by an emulsifier region. Therefore, nanoemulsions are limited to only hydrophobic components (e.g., fat-soluble vitamins, CBD, or fish oil). The oil-based ingredients are blended with emulsifiers (e.g., surfactants) under high-pressure emulsifiers to stabilize the droplets. Although nanoemulsions are easier for the body to absorb compared to the oil itself, this technology is not without its downsides. In order to stabilize such dispersions, large amounts of surfactants are used, the majority of which are harsh chemicals commonly used in cosmetics. The nanoemulsions are thermodynamically unstable and kinetically stable liquid systems which means the stability may be lost upon changing the properties of the surrounding medium (e.g., pH, temperature, presence of other ingredients, etc.). The droplets are also prone to interacting with other compounds in the solution and coalescing to the walls of the container over time.

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Nanovesicles vs. Micelles

Micelles are thermodynamically stable liquids formed by mixing oil, water, and emulsifiers together. Similar to nanoemulsions, micelles can be used to encapsulate hydrophobic components. While nanoemulsions contain only spherical droplets of oil, micelles may contain particles that are spheroid or worm-like. In contrast to nanoemulsions, micelles can be formed spontaneously by simply bringing oil, water and surfactant together at a particular temperature without supplying any external energy, since they are thermodynamically stable systems. Although it is possible to create relatively stable and bioavailable formulations using micelles, they are limited to hydrophobic ingredients, do not mask the taste, and have no control over the release kinetics of the functional ingredients after consumption.

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Nanovesicles vs. Liposomes

Liposomes are hollow spherical encapsulations composed of a phospholipid lipid bilayer, usually composed of similar chemicals as micelles. The aqueous (i.e., hydrophilic) center of the sphere is surrounded by the lipid bilayer. Depending on the properties of the functional ingredients, they can be encapsulated either in the aqueous center of the liposome or within the hydrophobic shell. Compared to nanovesicle encapsulations, liposomes have a larger diameter, lower solubility, shorter shelf life, and can leak the encapsulated ingredients over time.

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CBD

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CBG
CBL
CBN
Terpenes

THC

– Delta-8
– Delta-9
– Delta-10

Ashwagandha (Withania somnifera)
Asparagine
Aspartic acid
Astragalus (Astragalus membranaceus)
Bacopa Monnieri
CDP Choline
Chaga (Inonotus obliquus)
Cordyceps extract
Curcumin extract
Cysteine
Damiana (Turnera diffusa)
Eleuthero (Eleutherococcus senticosus)
GABA
Ginger root
Ginkgo Biloba
Ginseng (Panax ginseng, Panax quinquefolius)
Gotu Kola extract
Holy Basil (Tulsi or Ocimum Tenuiflorum)
Kanna (Sceletium Tortuosum)
Kava (Piper Methysticum)
Lions Mane (fruiting bodies)
Maca (non gelatinized)
Maitake (Grifola fondosa)
Melatonin
Piracetam
Pyrroloquinoline Quinone (PQQ)
Reishi (Ganoderma lingzhi)
Rhodiola Rosea
Saffron Extract (Crocus sativus)
Schisandra (Schisandra chinensis)
Sulbutiamine
Taurine
Turmeric
Turkey Tail (Trametes versicolor)
Tyrosine
Valerian root
Velvet Bean (Mucuna pruriens)

Ashwagandha
Asparagine
Aspartic acid
Astragalus
Bacopa Monnieri
CDP Choline
Chaga
Cordyceps extract
Curcumin extract
Cyesteine
Damiana
Eleuthero
GABA
Ginger root
Ginkgo Biloba
Ginseng
Gotu Kola extract
Holy Basil
Kanna
Kava
Lions Mane
Maca
Maitake
Melatonin
Piracetam
Pyrroloquinoline Quinone (PQQ)
Reishi
Rhodiola Rosea
Saffron Extract
Schisandra
Sulbutiamine
Taurine
Turmeric
Turkey Tail
Tyrosine
Valerian root
Velvet Bean

5-HTP
Acetyl L-Carnitine
Alanine
Arginine
Calcium
Chloride
Glutamic Acid
Glutamine
Glutathione
Glycine
Iron
L-Theanine
Lysine
Magnesium
Manganese
Melatonin
Phenylanine
Phosphatidylserine
Potassium
Selenium
Silica
Sodium
Tyrosine
Vitamin A
Vitamin B1 (thiamine)
Vitamin B12 (cobalamin)
Vitamin B2 (riboflavin)
Vitamin B3 (niacin)
Vitamin B5 (pantothenic acid)
Vitamin B6 (pyridoxine)
Vitamin B7 (biotin)
Vitamin B9 (folate)
Vitamin C
Vitamin D3
Vitamin E
Vitamin K
Zinc