
Without question, the beauty industry has witnessed astonishing growth over recent years due to an enhanced emphasis on self-care, evolving consumer preferences, social media presence, diversity, inclusivity and technological advancements. These influences have led to an enormous increase in the amount of beauty and personal care product offerings, the development of novel formulations, improvements in product performance, and an expansive increase in the selection of ingredients for manufacturing.
Log in to view the full article
Without question, the beauty industry has witnessed astonishing growth over recent years due to an enhanced emphasis on self-care, evolving consumer preferences, social media presence, diversity, inclusivity and technological advancements. These influences have led to an enormous increase in the amount of beauty and personal care product offerings, the development of novel formulations, improvements in product performance, and an expansive increase in the selection of ingredients for manufacturing.
There remains a preference and demand for natural ingredients. Traditional formulations that have contained non-biodegradable and “advisory” ingredients by today’s standards have been regenerated to meet current consumer demands. In addition, the shift towards exceptionally effective and sustainable skin care has prompted movement in legislation, marketing and consumer awareness.
Functional Ingredients & Cosmeceuticals
Although its current popularity is often viewed as a trend, the concept of functional ingredients is not new. Functional Ingredients are defined as materials that can perform a specific function or purpose. Functional cosmetics formulations must include ingredients that are recognized as safe and will provide desirable and beneficial effects. Contemporary formulations have extended beyond simplistic functions and may feature specific skin care benefits, in addition to their primary role.
The term cosmeceutical was coined by the late Dr. Albert Kligman who in 1984 defined a cosmeceutical as: “a topical preparation that is sold as a cosmetic, but has performance characteristics that suggest a pharmaceutical action.” This concept typically suggests that a skin care formula or ingredient provides therapeutic benefits to the skin above and beyond what would be seen within a simple formula. The U.S. Food and Drug Administration (FDA) has never truly embraced the term and as recently as 2020, reminded the industry that the term has no meaning under the law.1
A great deal of innovation has evolved since the inception of Kligman’s cosmeceutical concept. Today, functional skin care hails as a “modern archetype” utilizing innovative ingredient combinations with actives, antioxidants, indigenous botanicals, fermentation products and novel biotechnology.
Active Ingredients Defined
According to the FDA, an active ingredient is any component that provides pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or animals.2 Controversy continues regarding the active ingredients found within cosmeceuticals and skin care products, and in particular their mechanisms of action, formulation, optimal concentration, penetration and retention in the skin.
Although hundreds of skin care ingredients are described or marketed as “actives,” many are not officially recognized as such by the FDA (See FDA Active Ingredients List Sidebar). Cosmetic active ingredients have multiple functions and can be divided into preventive protective, regenerative and anti-inflammatory activities (See Cosmetic Active Ingredients List Sidebar).
FDA Active Ingredients List3
- Benzoyl peroxide
- Resorcinol
- Salicylic acid
- Sulfur
- Allantoin
- Calamine
- Cocoa butter
- Colloidal oatmeal
- Dimethicone
- Glycerin
- Zinc oxide
- Astringents
- Avobenzone
- Homosalate
- Octisalate
- Titanium dioxide
- Hydrocortisone
Cosmetic Active Ingredients List
- Retinol
- Retinaldehyde
- Lactic acid
- Glycolic acid
- Hyaluronic acid
- Beta-glucan
- Aloe vera
- Vitamin C
- Vitamin E
- Kojic acid
- Niacinamide
- Peptides
- Amino acids
- Growth factors
- Shea butter
- Linoleic acid
- Ceramides
- L-ascorbic acid
- Niacinamide
- Gingko Biloba
- Ginseng
- EGCG
- Soy isoflavones
Related: Ingredients 1001: Exploring the Significance of Ingredients
Fundamental Positioning
Most skin care cosmetic formulations are an oil-water emulsion (O/W), a water-oil emulsion (W/O) or a double emulsion (oil-water-oil or water-oil-water). From the delivery perspective, the W/O emulsion is much preferred, since the stratum corneum lipids favor the oil-soluble active ingredients. A primary consideration regarding the efficacy of a skin care product is the release of its actives.
Conversely, it is not only the concentration or “potency” of an active in a formulation, but the cohesiveness of the entire formulation including vehicles, delivery system, binders, etc., that lends to the product's efficacy. Additionally, the products subsequent penetration into the stratum corneum, passage into the epidermal strata, and metabolization, determines the bioavailability of active agents to carry out their intended functions.
From the cosmetic and dermatological point of view, the bioavailability of an ingredient is extremely important: it is the portion of active agent that is locally available for metabolization in the skin after the application that supports its efficacy. This is particularly difficult to gauge as the individual skin layers would require evaluation to confirm traces of an active ingredient that may be detectable.
According to Dr. Cornelia M. Keck at Marburg University Institute of Pharma¬ceutical Technology & Biopharmacy Medicinal, substances or cosmetic agents must transition into the skin barrier and channel the active substances specifically to where they are needed. For the active ingredient to reach the target, the destination and the route must be clearly defined.
Additionally, whether the active substance could or should enter the dermis and transition into circulation is of great significance. The function of active ingredients must present solubility, and the active ingredient molecules should diffuse easily from the formulation to the skin.
Regarding the penetration of active compounds, careful consideration must be given to identifying potential hypersensitivities, skin surface abnormalities and barrier status. The incorporation of skin needling, or an electrical or heat-activated modality, should be cautiously confirmed for its safety to be used in conjunction with actives as enhanced stimulation is plausible and should be anticipated with their use.
The Delivery
Delivery systems are mechanisms of transport for the protection, controlled and targeted delivery of active substances. A highly desirable function of a delivery system is its ability to enhance the penetration of active ingredients through the skin layers while controlling its concentration in the skin, and ultimately delivering actives to the superficial skin layers. Delivery systems also can protect sensitive active ingredients, while the product is stored by only releasing actives when it is applied to the skin, providing a controlled and targeted release.
Active compounds are generally sensitive to light, pH, oxygen and temperature, which can lead to degradation. Novel and innovative solutions have been designed to help maintain their effectiveness. Notably, the type of delivery system has greater significance than the active ingredient itself, as the delivery system “programs” the actual delivery of the ingredients.
Considerations include: the type of delivery system, delivery mechanisms, cohesiveness and the safety of ingredients and compounds. There are intercellular and trans follicular delivery methods of cosmetic compounds via epidermal penetration.
Intracellular Delivery
This route is the main transepidermal pathway and permits a direct viaduct through the SC to the epidermis, and potentially the dermis. Liberation, penetration, permeation, and potential absorption occur through the corneocytes and intercellular lipid matrix. As the stratum corneum features keratinized cells, intracellular lipids, fatty acids and cholesterol, lipid-soluble products, such as liposomes and nanotechnology, are well suited to protect active ingredients for permeation. A molecule utilizing the transcellular route must penetrate, diffuse and move through the corneocytes. Additionally, the molecule must also partition into and diffuse through the estimated four to 20 lipid lamellae between each of these cells.4
The transcellular route requires the integration of both hydrophilic and hydrophobic components, and to facilitate the passage of molecules through the SC, penetration enhancers may be utilized. Chemical enhancers are featured in many dermatological and cosmetic products to help enhance the dermal absorption of lipophilic and hydrophilic active ingredients. More than 350 chemicals have been demonstrated to enhance skin permeability including terpenes, sulfoxides, fatty acids, fatty alcohols, alcohols such as glycol, surfactants and urea. These enhancers aid in absorption and are believed to improve the solubility of actives within the SC or the intercellular lipid bilayers. Studies suggest other potential mechanisms for the effectiveness of enhancers including an adjustment and increase in the fluidity of the SC lipids, removal of intercellular lipids and dilation between the cornified cells, and the exfoliation of the SC, which may result in undesirable effects such as ineffective barrier function.5
According to pharmaceutical, cosmetic and organic chemist Dr. Hans Lautenschläger, the transport of substances and their respective droplet emulsion particle size ranges between 20 to 1μm (0.020 to 0.001 mm). Although emulsifier concentrations may be reduced, microemulsions may develop minuscule particle sizes so small that they can hardly be measured. While this reduction factor may ensure the excellent transport of an active substance, there is potential for disruption to the skin barrier by ingredients in a formula that if left on the skin for a period may provoke irritation. In the situation where high concentrations of petrolatum or mineral oils occlude the skin surface for a certain period, persistent swelling results in the stratum corneum leading to barrier disorders and a delayed regeneration of the skin. Alcohol products in high concentrations also result in barrier disorders, as they severely affect the osmotic balance of the skin.6
Liposomes
Liposomes are the most widely known cosmetic delivery system, are highly permeable, have a favorable storage capacity on the stratum corneum, and are considered a chemically active agent to the skin. Their phospholipid membranes can facilitate the passage of active ingredients across the SC, as they have a high affinity for the skin surface.
Liposome structures are classified according to their structure and the number of lipid bilayers (lamellae) and vesicle size. Their spherical sub-microscopic vesicles have diameters between 25 and 5000 nm and are composed of lipophilic and hydrophilic molecules. The liposome center consists of an aqueous cavity encapsulated by one or more biomolecular phospholipid sheets, each separated from the other by aqueous layers. The multifunctional properties of phosphatidylcholines lead to various lipids in liposomal technology: natural lecithin (egg or soybean lecithin) or synthetic lecithin (di-palmitoyl lecithin), and the most common is phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and phosphatidic acid.7,8
Substances that form structures like the barrier layers and are cohesive to the natural lipid matrixes are supportive to barrier homeostasis due to their comparable physical structure. Phosphatidylcholine (PC) is a well-researched and effective delivery agent that will spontaneously fuse with the barrier layers without affecting their physical structure. This enables the active agent molecules to transfer and dissolve releasing the encapsulated agents into the deeper skin layers. For this reason, liposomal products should be free of preservatives, perfumes and further potential allergens.9
Soy (isoflavone) phospholipids are cost-efficient, and many have their estrogenic metabolites extracted. The use of phytoestrogens has had both controversy and support in product formulation. Research has assessed topical soy-based applications on many parameters including skin aging, skin barrier, dryness, eczema, acne and erythema. Consideration must be given to the ratio significance of the phytoestrogen in a product, along with other ingredients in the product such as herbal extracts, antioxidants, additional lipids, etc. Genistein (soy phytocompound) has been suggested to inhibit the unwanted activation of protein kinases that would otherwise lead to collagen and elastin degradation. In addition, the phytoestrogen effects of soybeans have been suggested to improve skin aging, especially among women undergoing menopause.10,11
Nanoparticles
Nanotechnology originated within the realm of biotechnology and bioscience, and is well utilized in pharmacology from which the cosmetic industry has taken its cue. Nano-based products utilize a large variety of nanomaterials that are presented in different compositions, shapes and sizes. In cosmetic formulation, nanotechnology permits chemists to overcome many common limitations of products by enhancing penetration, improving the stability of ingredients, controlling the release of active ingredients, and formulas themselves functioning as active agents (See Safe Ingredients for Nanoparticle Formulation Sidebar).
Safe Ingredients for Nanoparticle Formulation
- Alpha tocopherol
- Argan oil
- Ascorbic acid
- Boswellia
- Butchers broom
- Ceramides
- Coconut oil (virgin)
- CoQ10
- Curcumin
- Titanium Dioxide
- Isoflavone
- Kiwi seed oil
- Lauric acid
- Lavender
- Linseed Oil
- Lutein
- Lycopene
- Mangosteen
- Pomegranate
- Propolis
- Quercetin
- Raspberry seed oil
- Resveratrol
- Rice brain oil
- Rosemary extract
- Rutin
- Vitamin A
- Vitamin E
Due to their specific composition, nanoparticles also have a high affinity to the SC and are viable transport systems for active agents to improve the ability of penetration. Nano dispersions are preparations with particles smaller than 1 µm (= 1000 nm), that permit the reduction or even elimination of additives such as emulsifiers, spreading substances and penetration enhancers.
Components used for the preparation of nano emulsions are generally recognized as safe (GRAS) and their smaller particle size provides higher stability and better suitability to carry active ingredients, and it also increases the shelf life of the product. The capsules of nanoparticles at best consist of the monolayers of phosphatidylcholine, and the encapsulated nanoparticles contain an oily nucleus. Solid nanoparticles develop a filmy layer on the skin surface connected with an occlusive condition featuring a “depot-like effect” from where active agents are released. This occlusive condition is also responsible for the increase of skin hydration.
Nanomaterials tend to adhere to the SC surface and accumulate in the corneocyte spaces, and follicles acting as depots for bioactive agents and increasing their concentration potential. Due to their nature nanoparticles have a specific capacity to assimilate oil soluble agents such as vitamin E, A, Coenzyme Q10, etc. Nanoparticles are invisible to the naked eye or under a standard microscope and can only be seen through electron microscope technology.12,13
Modern Ingredient Marvels
Neuropeptides
Neurocosmetics are cosmeceuticals that contain synthetic neuropeptides that interact with the nervous system through skin mediators. Skin responses are regulated by a neuroendocrine system found in the skin capable of initiating adaptation mechanisms through quick pathways (neural pathways) or slow pathways (humoral pathways), acting at both local and systemic levels. Neuropeptides can play a role in skin homeostasis by activating or inhibiting such mediators.
Peptides found in skin act by various mechanisms of action, such as being able to function as epidermal or nervous growth factors or as neurotransmitters. There is growing research on bioactive peptides aimed at investigating their uses in products developed for stimulating collagen and elastin synthesis and improving skin healing. Neurocosmetics are said to act with the central nervous system, being capable of stimulating the nerve endings of the skin, sending pleasure and well-being “feelings” to the hypothalamus, and causing the release of specific substances on the skin which improve the aspect of skin relief.
Skin cells release growth factors and proteins that bind insulin, which are synthetized from proopiomelanocortine (POMC), catecholamines, steroidal hormones, vitamin D, eicosanoids from fat acids, and retinoids from diet carotenoids. Skin has developed an autonomous system that responds to local and peripheral stress, which functions by making use of neurotransmitters and hormone peptides in a manner similar to the hypothalamus-hypophysis-adrenal axis.14
Growth Factors
Growth factors are considered regulatory proteins in the body that mediate signaling pathways inside and outside of cells and are recognized for their role in dermal wound repair. They are located in skin fibroblasts and are responsible for synthesizing collagen and the extracellular matrix. The pertinent growth factors in skin and fibroblasts are epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). Morphological aging and wound healing both stimulate the release of growth factors impacting biochemical pathways that are critical to repair the dermal matrix.
Growth factors utilized in products are obtained from either cultured human cells (stem cells derived from adipose tissue or the newborn umbilical cord) or genetically engineered microorganisms. Recombinant technology uses bacteria or yeast cultures that have been modified to include a DNA sequence for a specific growth factor. International Nomenclature Cosmetic Ingredient (INCI) names are used to indicate the presence of a growth factor in a cosmeceutical: EGF is human oligopeptide-1, PDGF is human oligopeptide-10, and FGF 9 is human oligopeptide-12.
One challenge for growth factors is their stability, the potential to keep them active at room temperature, with an anticipated shelf life. In the laboratory setting, most growth factors are stored at temperatures less than –20 °C to maintain stability. Enzyme-linked immunosorbent assay (ELISA) tests can be used to examine the stability of growth factors in finished formulations, but this testing is not routinely done.
Multiple clinical studies over the last 20 years show that topical application of preparations containing growth factors can stimulate collagen synthesis and thereby decrease the appearance of fine lines and wrinkles. Hydrophilic molecules larger than 500Da MW offer low penetration potential through the stratum corneum. Growth factors are large hydrophilic molecules greater than 15,000 Da MW that are unlikely to penetrate through the epidermis in a measurable quantity to produce pharmacologic effects.
The primary mechanisms by which the growth factors can potentially exert their effect on the dermal matrix is by penetration through hair follicles, sweat glands, or compromised skin followed by interaction with cells in the epidermis such as keratinocytes to produce signaling cytokines that affect cells deeper in the dermis. Research says that it is hard to separate the effects of a growth factor itself from the moisturizer vehicle without ELISA testing. In a non- pharmaceutical product, the growth factor and vehicle effect cannot be separated, and the growth factor is always used in conjunction with the vehicle. It is estimated that about 5% to 10% of the growth factor added in a formulation remains active at room temperature. Because growth factors are regulatory proteins, this may be enough to elicit an effect, but must be confirmed through more in-depth testing.15,16,17,18,19
Opportunities Through Science
Cosmetic science and biotechnology have created immense opportunities for enhanced cosmetic formulations and efficacious ingredients. These may be viewed as optimistic retailing and service opportunities, and may afford us a heightened platform to showcase our knowledge, skills and talents.
REFERENCES
- https://www.happi.com/contents/view_online-exclusives/2021-11-29/cosmeceuticals-do-not-exist/
- https://www.fda.gov/drugs/drug-approvals-and-databases/drugsfda-glossary-terms
- https://www.fda.gov/files/about%20fda/published/OTC-Active-Ingredient-By-Monograph-Category.pdf
- https://link.springer.com/chapter/10.1007/978-3-642-68682-5_7
- https://biomeddermatol.biomedcentral.com/articles/10.1186/s41702-020-0058-7
- https://dermaviduals.de/english/publications/special-actives/precious-load-transport-of-active-agents.html
- https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1468-2494.2008.00416.x
- https://dermaviduals.de/english/publications/special-actives/liposomes.html
- https://dermaviduals.de/english/publications/special-actives/active-agents-liposomes-nanoparticles-co.html
- http://dx.doi.org/10.13040/IJPSR.0975-8232.14 (1). 41-49
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299547/
- https://dermaviduals.de/cms/upload/Publikationen_english/KI-7-06-Wirkstofftransport-engl.pdf
- https://www.researchgate.net/publication/353204127_Current_Advances_of_Nanocarrier_Technology-Based_Active_Cosmetic_Ingredients_for_Beauty_Applications
- https://www.mdpi.com/2079-9284/5/1/21
- https://www.dermatologytimes.com/view/the-growing-popularity-of-growth-factors
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423211/
- http://www.boonaye.com/korean/images/GF_article.pdf
- https://onlinelibrary.wiley.com/doi/full/10.1111/jocd.15644
- https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-020-01502-1
ADDITIONAL RESOURCES
- https://edu.rsc.org/download?ac=508605
- https://www.personalcarecouncil.org/wp-content/uploads/2021/02/Conventions2021_v1.pdf
- https://www.fda.gov/cosmetics/cosmetic-products-ingredients/cosmetic-ingredients
- https://dermaviduals.de/english/publications/books/corneotherapy-link-between-dermatology-and-cosmetics.html
Erin Madigan-Fleck, NMD, CDT, LMC, LEI, has more than 35 years of experience in the aesthetic and natural health industry. She is a naturopathic medical physician with a private practice, Naturophoria, in Atlanta. She is a member of the American Society for Nutrition and serves on the Education Commission for the International Association for Applied Corneotherapy. She the owner and founder of DermaEducationTV Post Graduate Esthetic Training and the Scientific Esthetics Symposium.