Author: james.runkle@drummondst.com

Introduction

As the body’s first defense against the elements, skin is frequently exposed to electromagnetic radiation from the Sun, which can lead to a variety of detrimental conditions such as photoaging, photoimmunosuppression, and photocarcinogenesis. Reactive oxygen species are largely responsible for the initiation of these disease states in skin and are mostly due to exposure to ultraviolet light, but have also been shown to result to some extent from the absorption of visible and infrared light. Considerable efforts have also been made to better understand the effects of pollution on the skin from a free radical and reactive oxygen species point of view.

Antioxidants

The use of antioxidants in various skin treatments is a sound approach to improve the overall health state of skin [1]. This statement is supported by a wealth of research conducted over the last several decades toward better understanding how antioxidants mitigate the effects of solar radiation. Topical application of antioxidant-containing products reduces the deleterious effects of solar radiation exposure of the skin.

While some antioxidants may offer some photoprotection as a solar filter, the majority of their mechanisms are through their antioxidant capacity or immunomodulating effects. Some of the most common antioxidants in skin care formulations are vitamin E, vitamin C, and coenzyme Q. Historically, these were probably the most studied antioxidants due to their importance in the endogenous antioxidant system.

Equally important are a vast majority of botanical extracts, which are chock-full of phyto-antioxidants. In recent years, research has focused on understanding the antioxidant behavior of polyphenols in an attempt to harness their protective properties for skin. In some cases, specific polyphenols are used in formulation while in others the extract is directly added.

Topical Application of Antioxidants

Topical application of antioxidants is the most straightforward approach to fortify the skin. As compared to dietary intake of antioxidants, in many cases topical application allows: (1) greater concentrations to reach tissues, (2) greater tissue specificity, and (3) reduced side effects to other organs. Unfortunately, not all antioxidants (e.g., from extracts) easily cross the stratum corneum barrier. The fact that some antioxidants are not able to penetrate the skin could be considered a positive toxicological benefit. Skin permeation and antioxidant stability can be enhanced by utilizing state-of-the-art delivery systems.

One of the major factors with antioxidant stability in skin care formulations stems from the need to prevent oxidation within the formulation and also to deliver to the skin an active antioxidant that is bioavailable. In many cases, formulations are based on carrier systems in which oxidation can occur in the oil phase, water phase, or at the interface. More often than not, oxidation occurs at the interface. Some of the hurdles facing formulators in the antioxidant arena are a result of stability issues with antioxidants that are intended to be delivered to skin.

Antioxidant Carrier Systems

The use of carrier systems represents a real asset for the delivery of antioxidant to skin and can include various types of emulsion, vesicular, or lipid particle systems.

Emulsions systems

These systems are dispersions of oil and water and can refer to microemulsions, nanoemulsions, and Pickering emulsions. Microemulsions and nanoemulsions are characterized by the dispersion size of the emulsified phase, while Pickering emulsions refer to a type of emulsion that is stabilized by solid particles.

Vesicular systems

These systems consist of liposomes, phytosomes, transferomes, ethosomes, and niosomes. Liposomes are the most popular vesicular system used in personal care applications and are composed of concentric layers of phospholipid bilayers spherically shaped with a hollow center for the active ingredient. Phytosomes are vesicles of phospholipids that have high affinity for phytocompounds, such as polyphenols. Transferosomes are lipid vesicles that consist of fatty acids and a small amount of ethanol. They are more elastic than liposomes, which improves their deposition characteristics. Ethosomes are lipid vesicles that contain even greater amounts of ethanol, yielding a more flexible vesicle. Niosomes are lamellar vesicles based on nonionic surfactants. Due to the nature of the surfactants in niosomes, crossing the stratum corneum is more facile than in the case with other vesicles.

Lipid particle systems

These systems consist of lipid microparticles and lipid nanoparticles. Lipid microparticles are created by a process known as microencapsulation where a small solid or liquid droplet is surrounded with a thin layer of shell. Lipid nanoparticles are further categorized as solid lipid nanoparticles and nanostructured carriers. Solid lipid particles consist of a lipid system in the solid state at room temperature with a thin surface coating on the outside as a stabilizer. Nanostructured lipid carriers, on the other hand, are more complex and contain lipids both in the solid and fluid phase. Typically, such systems can increase the stability of antioxidants and their permeation efficacy to skin as well as reduce irritation. The reader is referred to a review by Pol and Patravale for a nice introduction to the subject [2].

Nanoparticle and Nanocarriers

Nanoparticles and nanocarriers continue to be at the forefront of skin care research for their potential at stabilizing and delivering antioxidants to the skin. For example, gold nanoparticles are known for their anti-inflammatory, antiaging, and wound healing properties in skin care. A recently published study demonstrated how polyphenols from an aqueous extract can be used to reduce metal salts—in this case gold—into nanoparticles [3]. In another study, gold nanoparticles wrapped with chitosan were used to stabilize ellagic acid [4]. In both cases, green technology was used to fabricate the nanoparticle structures.

Nanoencapsulation is another area that shows much promise for the delivery of antioxidants to skin. Lipid-core nanocapsules containing resveratrol and lipoic acid have enhanced chemical stability and photostability as compared to the non-encapsulated forms of the molecules [5]. TiO₂ is a nanoparticle found in many sun protection products. It functions by scattering incoming UV rays from the Sun and preventing photodamage to the skin. Researchers at Sabanci University in Istanbul found enhanced cellular penetration and antioxidant properties of quercetin-TiO₂ nanoparticles, as compared to quercetin alone, in studies carried out on fibroblast cell cultures [6].

Concluding Remarks

Some of the challenges with the conventional delivery of antioxidants stems from their poor solubility, limited shelf-life stability, compromised photostability, and low degree of skin permeability. Delivery systems enhance the ability of antioxidants to carry out their function. Conventional systems used to deliver antioxidants consist of emulsion, vesicular, or lipid particle systems. In recent years, a great deal of interest has evolved in using nanoparticles as stabilization enhancers and delivery agents for antioxidants. Nanoencapsulation also offers much promise and has been shown to enhance the chemical stability and photostability of antioxidants.

References

1. McMullen, R., Antioxidants and the Skin. 2nd ed. 2019, Boca Raton: CRC Press.
2. Pol, A. and V. Patravale, Novel lipid based systems for improved topical delivery of antioxidants. Household and Personce Care TODAY, 2009(4): p. 5-8.
3. Haddada, M., et al., Assessment of antioxidant and dermoprotective activities of gold nanoparticles as safe cosmetic ingredient. Colloids Surf B Biointerfaces, 2020. 189: p. 110855.
4. Gubitosa, J., et al., Multifunctional green synthesized gold nanoparticles/chitosan/ellagic acid self-assembly: Antioxidant, sun filter and tyrosinase-inhibitor properties. Mat Sci Eng C, 2020. 106: p. 110170.
5. Davies, S., et al., Simultaneous nanoencapsulation of lipoic acid and resveratrol with improved antioxidant properties for the skin. Colloids Surf B Biointerfaces, 2020. 192: p. 111023.
6. Birinci, Y., et al., Quercetin in the form of a nano-antioxidant (QTiO₂) provides stabilization of quercetin and maximizes its antioxidant capacity in the mouse fibroblast model. Enzyme Microb Tech, 2020. 138: p. 109559.

Roger L. McMullen, Ph.D. – BIO

Dr. Roger McMullen has over 20 years of experience in the personal care industry with specialties in optics, imaging, and spectroscopy of hair and skin. Currently, he is Principal Scientist in the Material Science department at Ashland Specialty Ingredients G.P. Roger received a B.S. in Chemistry from Saint Vincent College and completed his Ph.D. in Biophysical Chemistry at Seton Hall University.

Roger actively engages and participates in educational activities in the personal care industry. He frequently teaches continuing education courses for the SCC and TRI-Princeton. In addition, Roger is an Adjunct Professor at Fairleigh Dickinson University and teaches Biochemistry to students pursuing M.S. degrees in Cosmetic Science and Pharmaceutical Chemistry. Prior to pursuing a career in science, Roger served in the U.S. Navy for four years on board the USS YORKTOWN (CG 48). He is fluent in Spanish and Catalan.

Cosmetic chemists are an innovative, curious, and creative group of scientists, continually looking to formulate the most effective and pleasing products for the world’s consumers. Yet when asked to create the galenic forms most often requested by marketing – creams and lotions – the “default emulsion” is almost always oil-in-water (O/W). While O/W systems offer good sensory properties and ease of manufacturing, the primary alternative system – water-in-oil (W/O) – offers distinct advantages, among them long-lasting adherence to the skin and improved water resistance. So why isn’t W/O used more often? Because (a) it is difficult to create a stable W/O system, and (b) the esthetics of a W/O emulsion are often undesirable (sticky, tacky, thick…).

Let’s cover some key concepts to enhance stability when formulating W/O emulsions:

1. When making W/O emulsions, high energy is required

Why do we need high energy when making a W/O emulsion? High energy brings several benefits to your W/O system, altogether contributing to a stable emulsion:

1. Creates high energy dissipation rates ^1,2
2. Controls particle size of the dispersed phase of the emulsion ^1,2
3. Reduces interfacial tension ^1,2

To achieve the desired results, one may use high-energy equipment such as a rotor stator/homogenizer or a deflocculator at moderate to high shear.

Let’s take a closer look at each…

A) Dissipation rate refers to the rate of conversion of turbulence into heat by molecular velocity.

Here is a simplified energy flow chart when you are creating a W/O emulsion:

Turbulence, initiated by the high-shearing rotor stator, transfers its energy into kinetic energy within the W/O system. That energy of motion is converted into the large velocity gradients of the dispersed droplets of various sizes. And finally, the energy of the rapidly moving particles is converted into heat through dissipation.²

This is a very simplified flowchart, as there are many other variables involved, but the take-home message here is that the higher the conversion of energy into heat, the higher the dissipation energy, the more kinetically stable emulsion. Essentially, we do not want any energy left in the emulsion, especially in those water droplets because that can lead to instability.

B) The energy applied when creating a W/O emulsion affects the particle size of the internal phase of an emulsion.

As mentioned before, high energy processes will use rotor stators/homogenizers, while a low energy process may use simpler blades (turbine stirrer, propeller, or blade stirrer). If you use high energy, you will achieve a finer, more evenly dispersed emulsion, which is exactly what you want, as this is more stable.

But if homogenization is too mild, due to your equipment and/or shearing speed, your W/O emulsion will be highly poly-dispersed, meaning, there will be a wide size distribution in the dispersed droplets, which can lead to instability. 

C) And finally, we need to use high energy with W/O systems because it reduces the interfacial tension (energy present at the water-oil interface).

This benefit is a result of the other two: The more heat that is given off, the less energy and mobility in the dispersed water phase. And the smaller the average droplet size of the dispersed phase, the more the stability increases. Altogether, there is less energy remaining at the water-oil interface, so water droplets are less likely to coalesce and will remain stable within the continuous oil phase. 

2. Electrolytes must be used

Electrolytes – inorganic salts such as magnesium sulfate or sodium chloride – must be present in the emulsion because they will stabilize your system through various mechanisms of action. For example, NaCl has been shown to decrease the particle size through electrostatic and steric repulsion in the droplets.³ CaCl₂ has proven to decrease attractive forces between water droplets.³ And MgCl₂ can reduce interfacial tension and enhance interfacial film strength.³

Each of these mechanisms may prevent one or more of the following from happening.

1) Ostwald ripening, also referred to as disproportionation, is caused by the difference in solubility in emulsion droplets. Smaller droplets are more soluble than larger ones, and with prolonged time, the smaller droplets tend to diffuse in the bulk and are deposited on larger droplets. Therefore, larger droplets eventually grow at the expense of smaller ones. Adding salts will counterbalance the driving force for Ostwald ripening, which is related to the total pressure and pressure in the droplets.³

2) Sedimentation is another unstable condition where there is no change to the droplet size, but droplets move to the bottom. The addition of various salts could improve stability by decreasing particle size and reducing the interfacial tension. Salts can allow for tighter packing of surfactant molecules at the O/W interface.³

3) Coalescence is when droplets join, creating larger sized droplets with water separation at the bottom. Adding salts will reduce the attractive forces between water droplets, which will reduce their collision frequency, and thereby prevent droplet coalescence and increase emulsion stability.³

3. Depending on the emulsifier, the polarity of the oils used must be specific

Unlike O/W systems, the polarity of the oils used in the oil phase has an outsized influence on the stability of the emulsion, and the performance of high-polarity vs. low-polarity oils will be significant. This is because of the “like dissolves like” rule. In general, chemicals of similar polarities demonstrate better interaction. If the lipophilic tails of your emulsifier are polar, perhaps having esters or hydroxyl groups in its carbon backbone, for example, then the emulsifier is better suited in an oil phase of medium to high polarity. The opposite holds true as well. If the polarity of the oil phase does not match that of the emulsifier, the emulsion will not be stable.

Now, let’s talk briefly about the esthetics of W/O emulsions

W/O emulsions are often tacky or draggy, leaving an unpleasant skin feel and an uncomfortably thick layer of product. Also, as W/O systems are often used with pigments, many common emulsifiers do not have the correct compatibility with the wide variety of pigments used today, resulting in non-homogenous dispersions of the pigments within the emulsion. Many traditional W/O emulsifiers were not designed to address issues of skin feel or pigment dispersion, but modern advances in esterification chemistry allow for the creation of a new generation of emulsifiers that provide perceptibly improved sensory characteristics.

It can be suggested that the use of an emulsifier based on polyglycerol chemistry is especially suited to W/O systems due to enhanced stability resulting from large polar headgroups. (Incidentally, polyglycerol chemistry is considered “green” and advantageous when formulating natural or clean products…) Esterifying a polyglycerol backbone with other esters will significantly effect both skin feel and pigment dispersion properties; for example, the use of a ricinoleic acid ester could provide fluidity and improved skin feel, while the use of a hydroxystearic acid ester could improve the dispersibility of both coated and uncoated pigments.

With these concepts in mind, formulating a W/O emulsion can result in an elegant product satisfying the end consumer while meeting the requirements of marketing, allowing the creativity of the chemist to move “beyond the box” of traditional cosmetic emulsions.

References

1. Turbulence and multiphase flow. http://www.lowshearschool.com/?page_id=16919
2. The effect of shear on oil-water mixture. http://www.lowshearschool.com/?page_id=16933
3. Zhu Q , Pan Y, Jia X, Li J, Zhang M, Yin L. Review on the stability mechanism and application of water-in-oil emulsions encapsulating various additives. Comprehensive Reviews in Food Science and Food Safety, 18 (6): 1660-1675, 2019

Leor Fay Tal is the Technical Marketing Leader for the Personal Care division of Gattefossé USA. She delivers information on trends and consumers, provides technical marketing support to the company’s sales teams and agents across North America, Canada, and Mexico, and works to promote knowledge and understanding of the company’s ingredients. Prior to Gattefossé, Leor Fay had worked in the R&D Powder Laboratory and then as the Raw Material Regulatory Affairs Specialist at MANA Products. Leor Fay is also an active member of the NYSCC. She organized the April 2018 event Cosmetics in the Middle East, A Regulatory Perspective and now serves as the Secretary for the executive board.

Ben Blinder is the Senior Director for Gattefossé USA – Personal Care Division, where he is responsible for the strategic direction and performance of the cosmetic business for Gattefossé in the US and Mexico. Ben holds a chemical engineering degree from Lehigh University and has been working in the personal care industry for 32 years, with extensive experience in strategic and long-range planning, sales and technical management, and new technology search/discovery.  Ben also serves on the NYSCC Scientific Committee.