Why Nanoemulsions Are Important

Nanoemulsions are a type of emulsion that consist of tiny droplets of one liquid dispersed within another liquid, typically with a droplet size range of 20 to 200 nanometers although most have an upper range of 100 nm (Gupta et al., 2016). They are usually prepared as isotropic dispersions of stabilized water and oil phases using emulsifiers (Dasgupta et al., 2019).  

They are characterized by their small droplet size, high stability, and transparent or translucent appearance. They also have a lower viscosity.

Nanoemulsions are also frequently known as mini-emulsions, fine-dispersed emulsions and submicron emulsions.

Structure of Nanoemulsions

A nanoemulsion contains between 5 and 20% oil or lipids in droplets in the case of O/W emulsions. It may occasionally be significantly larger in the proportion of up to 70%. Fractions are derived from coconut oil, sesame oil, soybean oil, safflower oil etc.

Nanoemulsions are created by using specialized techniques such as high-pressure homogenization, ultrasonication, or microfluidization. These methods break down the larger oil or water droplets into smaller droplets, resulting in a highly dispersed and stable system.

High-pressure Homogenization

A technique using a high-pressure homogenizer or piston homogenizer that produces nanoemulsions of extremely low particle size – usually up to 1 nm (Asua, 2002; Anton et al., 2008). The efficiency of droplet disruption within a high-pressure homogenizer usually increases as the viscosity of the disperse phase decreases (Walker et al., 2017).

Ultrasonic Emulsification

A process which is excellent for reducing droplets in size. All the energy comes from sonotrodes contained in a sonicator probe. This uses a  piezoelectric quartz crystal which can expand and contract in response to alternating electric voltage. The tip of the sonicator is in contact with the liquid and produces a high energy mechanical vibration and cavitation soon follows. Cavitation forms and collapses vapour cavities in the liquid. As a result of this energy input the emulsion droplet size can fall to as low as 0.2 microns in diameter.

Phase Inversion Temperature (PIT) Method

 Phase changes are produced by applying a higher temperature to a microemulsion (El-Aasser et al., 1986; Pouton, 1997).   

Spontaneous Emulsification

A more passive method is spontaneous emulsification (Tadros et al., 2004; Solans et al., 2005). It is regularly employed in nanoemulsion creation. This requires:-

  1. Preparation of an homogeneous organic solution consisting of oil and lipophilic surfactant in water miscible solvent and hydrophilic surfactant,
  2. Injection of the organic phase into an aqueous phase under continuous magnetic stirring which forms an o/w emulsion
  3. The aqueous phase is removed by evaporation under reduced pressure.

In many cases, the lipid phase is mixed with 2% w/w emulsifier such as Tween 80 and then with water or buffer solutions. A coarse emulsion is produced using a high shear mixer followed by ultrasonication to reduce the droplet size further. Ultrasound would have a power of 400W and frequency of 24 kHz equiped with 22mm sonotrodes set at an amplitude of 30 microns.

Stability

The small droplet size of nanoemulsions gives them unique properties and advantages over traditional emulsions. The increased surface area of the droplets enhances their kinetic stability, preventing phase separation or coalescence (Devarajan & Ravichandran, 2011). Another way of describing this is to confer stability against creaming or sedimentation. We should not see droplet aggregation in nanoemulsions through coalescence flocculation because of their relatively small particle size (Tadros et al., 2004).

Creaming is what you see on the top of milk – coalesced fat and protein globules which have become unstable and coalesced at the top. The reason for the stability is that Brownian motion and consequently the diffusion rate are higher than the sedimentation rate or creaming rate induced by gravitational forces. This stability allows for improved shelf life and resistance to creaming or sedimentation.

The stability of a nanoemulsion however is only feasible when it is not subject to heating, or freeze thawing. Pasteurization can destabilise any emulsion including nanoemulsions. A change in pH can also be destructive. That was noted for a system of encapsulated carotenoids (McClements, 1999).

Breakage Of a Nanoemulsion

A nanoemulsion is destabilised when Ostwald ripening or molecular diffusion which has arisen from emulsion polydispersity and the difference in solubility between small and large droplets. 

Their properties are based mostly on their thermodynamically stability because the droplet suspension is so stable. They have a kinetic stability which lasts for many months, they are stable when diluted and robust enough to withstand temperature fluctuations which would normally cause them to separate into two phases. They are unlike their counterparts the microemulsions which have thermodynamic stability. Emulsions are generally thermodynamically unstable because the free energy of emulsion formation ( (ΔGf) is greater than zero. 

Measurement of Droplet Size

Droplet size distribution is measured using  dynamic light scattering (DLS), but also by transmission electronic microscopy (TEM) coupled with negative staining, or cryo-TEM, freeze-fracturing followed by replication plus TEM, or capillary hydrodynamic fractionation (CHDF). Greater detail is obtained  on surface particle characterization using surface potential characterization. The surface morphology is determined using specific approximations of electrophoretic models (e.g. soft particle model). Small-angle neutron scattering (SANS) or small-angle X-ray scattering (SAXS) is useful for investigating the internal morphology of such colloidal objects.

Applications for Nanoemulsions

Nanoemulsions have applications in various industries including pharmaceuticals (Singh et al., 2017), cosmetics, food, and beverage. In the pharmaceutical field, nanoemulsions can be used to improve the delivery of drugs, as the small droplet size enables enhanced solubility and bioavailability. In the cosmetics industry, they are utilized for formulations such as lotions, creams, and serums, as they provide a smooth and lightweight texture and enhance the absorption of active ingredients into the skin.

A typical colloidal carrier system for ceramides that can be applied to the skin uses a positively charged oil/water nanoemulsion (PN). In the example phytosphingosine containing PN was a colloidal carrier for ceramide IIIB (CIIIB; N-stearoyl-4-OH-sphinganine) and the stratum corneum (SC) lipids (PPNSC) such as ceramide III (CIII), cholesterol, and palmitic acid (Yilmaz et al., 2005). .

In the food and beverage industry, nanoemulsions can be used to encapsulate flavors, nutrients, or bioactive compounds, improving their dispersibility and stability. This can lead to enhanced sensory properties and increased bioavailability of these substances in food and beverage products.

Colour nanoemulsions using beta-caroteine and lutein are available. Evaporation emulsification was used to create β-carotene oil-in-water nanodispersions (Tan & Nakajima, 2005 a, b). The mean diameter of any droplet was between 85 and 140 nm. The beta-carotene, even on storage at chill temperature degraded over time.

Yuan ( 2008 a,b) also reported losses of carotene but less so compared to the nanoemulsion of Tan & Nakajima.

Pascual-Pineda et al., (2015) studied the stability of paprika oleoresin prepared using homogenization and then high-power ultrasound. The oleoresin was dispersed in a surfactant solution which in this instance was Tween 40, Span 20 or a mixture of both. A more stable nanoemulsion is generated with a mixture and can create smaller particle sizes rather than when just one emulsifier is used (Gullapalli & Sheth, 1999). 

A clear yellow-orange nanoemulsion for use in beverages was created using spontaneous emulsification of lutein. This nanoemulsion had a composition of 10 wt% oil phase (0.12 wt% lutein + 9.88 wt% MCT-Medium-Chain Triglycerides), 10 wt% Tween 80 and 80% wt% aqueous phase. The emulsion had a shelf-life of 1 month when stored at ambient temperature before droplet aggregation occurred. There was colour fading in the lutein although this can be ameliorated for by inclusion of an antioxidant such as vitamin E.

Plant-based essential oils are now a common feature of the food protection scene. They are regularly encountered now in the food industry and in clinical applications (Jamir et al., 2013). 

A recent example was the preparation of oregano essential oil and resveratrol as a nanoemulsion which was loaded into an edible coating. The coating was pectin used to preserve pork loin stored in modified atmosphere packaging.(Xiong et al., 2020) which was high oxygen (HOMAP). The nanoemulsion was stable at 4°C for 15 days. The improved performance on preserving the meat was down to the enhanced preservative function produced by the smaller droplet size. The use of essential oils with strong flavours such as sage and oregano has often compromised the flavour of the preserved meat because they have such an intense and bitter flavour. Using a nanoemulsion helps minimise the sensory impact.

A beverage application was produced using apple juice. In this example, an antimicrobial was introduced into a nanoemulsion that was stored in apple juice. The nanoemulsion contained lemon grass and mandarin essential oils which inactivated Escherichia coli. However, nanoemulsions in complex beverages have lower antimicrobial activity than in water but there is scope for their use because the nanoemulsion minimises flavour impact from the oil. A nanoemulsion formulated using the apple juice-based beverage offered a high antioxidant activity, with values of up to 400 mg Eq. Trolox/mL, probably due to the presence of polyphenols.

Parenteral Nanoemulsions

In the pharmaceutical industry, these nanoemulsions are used to deliver drugs with lower bioavailability. They are used as an alternative to vesicles and liposomes. It means that they can also be used like cosmetic creams to deliver drugs through a dermal and transdermal route (Rai et al., 2018). They improve the bioavailability of drug and can be formulated into creams, foams and liquids including sprays.

In clinical applications, Mentha piperita essential oil has been applied as a nanoemulsion to treat human breast cancer cell lines (Abedinpour et al., 2021).

In terms of drugs, examples include chlorambucil which is a liophilic anticancer drug. This nanoemulsion is made using ultrasonication and high pressure homogenization to treat breast and ovarian carcinoma. A similar process has been used to prepare tamoxifen for the treatment of breast cancer.

Major Producers of Colour Nanoemulsions

  1. GNT Group: The GNT Group is a leading global provider of natural color ingredients, including color nanoemulsions, for various applications, including beverages.
  2. Sensient Technologies Corporation: Sensient is a multinational corporation that offers a wide range of natural and synthetic color solutions, including nanoemulsions, for beverages and other industries.
  3. Chr. Hansen Holding A/S: Chr. Hansen is a company that specializes in natural solutions, including colorants, for the food and beverage industry, and they may have color nanoemulsions in their product portfolio.
  4. Döhler GmbH: Döhler is a global producer of natural ingredients and ingredient systems for the food and beverage industry, including color nanoemulsions.
  5. Symrise AG: Symrise is a company that provides flavor, fragrance, and color solutions for various applications, and they might offer color nanoemulsions for beverages.

Overall, nanoemulsions offer exciting possibilities for the development of innovative formulations in various industries, owing to their small droplet size, improved stability, and potential for enhanced delivery and absorption of active ingredients.

References

Abedinpour, N.Ghanbariasad, A.Taghinezhad, A., & Osanloo, M. (2021). Preparation of nanoemulsions of Mentha piperita essential oil and investigation of their cytotoxic effect on human breast cancer linesBioNanoScience11, pp. 428436 (Article)

Akhtar, J.Siddiqui, H. H.Fareed, S.BadruddeenKhalid, M.Aqil, M. (2016). Nanoemulsion: For improved oral delivery of repaglinideDrug Delivery23, pp. 20262034 (Article).

Anton, N., Benoit JP, Saulnier, P. (2008) Design and production of nanoparticles formulated from nano-emulsion templates-a review. J Control Release 128 pp. 185–199 (Article)

Ashaolu, T. J. (2021). Nanoemulsions for health, food and cosmetics: A reviewEnvironmental Chemistry Letters19, pp. 33813395 (Article).

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Aswathanarayan, J. B., & Vittal, R. R. (2019). Nanoemulsions and their potential applications in food industryFrontiers in Sustainable Food Systems3, 95 (Article).

Dasgupta, N., Ranjan, S. & Gandhi, M. (2019) Nanoemulsions in food: market demand. Environ Chem Lett 17, pp. 1003–1009 (Article)

Devarajan, V. & Ravichandran, V. (2011). Nanoemulsions: as modified drug delivery toolInternational Journal of Comprehensive Pharmacy4, pp. 1– 6.

El-Aasser, M.S., Lack, C.D., Vanderhoff J.W., Fowkes, F.M. (1986) Miniemulsification process-different form of spontaneous emulsification. Coll. Surf. 29 pp. 103–118

Gullapalli, R.P. & Sheth, B.B. (1999). Influence of an optimized non-ionic emulsifier blend on properties of oil-in-water emulsionsEuropean Journal of Pharmaceutics and Biopharmaceutics48, pp. 233– 238.

Jamir, Y., Bhushan, M., Sanjukta, R., & Robindro Singh, L. (2024). Plant‐based essential oil encapsulated in nanoemulsions and their enhanced therapeutic applications: An overview. Biotechnology and Bioengineering 121(2) pp. 415-433

McClements, D.J. (1999). Food Emulsions: Principles, Practices and Techniques. Pp. 300– 342Boca Raton, FL, USA: CRC Press, Taylor & Francis group.

Molet-Rodríguez, A., Turmo-Ibarz, A., Salvia-Trujillo, L., & Martín-Belloso, O. (2021). Incorporation of antimicrobial nanoemulsions into complex foods: A case study in an apple juice-based beverage. Lwt141, 110926 (Article).

Pouton, C.W. (1997) Formulation of self-emulsifying drug delivery systems. Adv Drug Deliv. Rev. 25 pp. 47–58

Rai, V. K., Mishra, N., Yadav, K. S., & Yadav, N. P. (2018). Nanoemulsion as pharmaceutical carrier for dermal and transdermal drug delivery: Formulation development, stability issues, basic considerations and applications. Journal of controlled release270, pp. 203-225.

Singh, Y., Meher, J. G., Raval, K., Khan, F. A., Chaurasia, M., Jain, N. K., & Chourasia, M. K. (2017). Nanoemulsion: Concepts, development and applications in drug delivery. Journal of Controlled Release252, pp. 28-49 (Article).

Solans, C., Izquierdo P, Nolla J, Azemar N, Garcia-Celma MJ (2005) Nanoemulsions. Curr Opin Coll Interface Sci 10 pp. 102–110 (Article)

Tadros, T., Izquierdo P, Esquena J, Solans, C. (2004) Formation and stability of nano-emulsions. Adv. Coll. Interface Sci. 108 pp. 303–318 (Article).

Tan, C.P. & Nakajima, M. (2005a). Effect of polyglycerol esters of fatty acids on physicochemical properties and stability of β-carotene nanodispersions prepared by emulsification/evaporation methodJournal of the Science of Food and Agriculture85, pp. 121– 126.

 Tan, C.P. & Nakajima, M. (2005b). β-Carotene nanodispersions: preparation, characterization and stability evaluationFood Chemistry92, pp. 661– 671

Walker, R., Decker, E. A., & McClements, D. J. (2015). Development of food-grade nanoemulsions and emulsions for delivery of omega-3 fatty acids: Opportunities and obstacles in the food industry. Food & Function6(1), pp. 41-54

Walker, R. M., Gumus, C. E., Decker, E. A., & McClements, D. J. (2017). Improvements in the formation and stability of fish oil-in-water nanoemulsions using carrier oils: MCT, thyme oil, & lemon oil. Journal of Food Engineering211, pp. 60-68.

Xiong, Y., Li, S., Warner, R. D., & Fang, Z. (2020). Effect of oregano essential oil and resveratrol nanoemulsion loaded pectin edible coating on the preservation of pork loin in modified atmosphere packaging. Food Control114, 107226 (Article).

Yilmaz, E., & Borchert, H. H. (2005). Design of a phytosphingosine-containing, positively-charged nanoemulsion as a colloidal carrier system for dermal application of ceramides. European Journal of Pharmaceutics and Biopharmaceutics60(1), pp. 91-98

Yuan, Y.Gao, Y.Mao, L. & Zhao, J. (2008a). Optimisation of conditions for the preparation of β-carotene nanoemulsions using response surface methodologyFood Chemistry107, pp. 1300– 1306

Yuan, Y.Gao, Y.Zhao, J. & Mao, L. (2008b). Characterization and stability evaluation ofb-carotene nanoemulsions prepared by high pressure homogenization under various emulsifying conditionsFood Research International41, pp. 61– 68   

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