Leslie Rank, PhD, Global Product Development Lead of Facial Treatment Products, and Rachel Bechtel, Senior Scientist on the Facial Cleansing Product & Process Innovation Team at Kenvue, spoke to dermatology residents at The George Washington University’s first Lab to Label Conference, about the formulation of popular products including dark spot actives, vitamin A derivatives, and cleansers. Below, we highlight key takeaways from their discussion.
Dark Spot Actives
Addressing dark spots or hyperpigmentation is one of the most common concerns raised by patients. From a formulation standpoint, numerous topical agents are available, each acting at different steps along the dark spot formation pathway, preventing increases in melanin synthesis, inhibiting the melanin production process, and/or treating existing dark spots. Dr. Rank explained how each of these individual agents functions.
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- Vitamin C targets dark spots by neutralizing free radicals to combat oxidation and by inhibiting tyrosinase, the rate-limiting enzyme of melanin production
- Tranexamic Acid inhibits UV-induced tyrosinase activity and microphthalmia-associated transcription factor (MITF), a regulator of melanogenesis
- Butylresorcinol inhibits tyrosinase as well as tyrosinase-related protein-1 (TRP-1), another protein involved in melanogenesis
- Niacinamide blocks the transfer of melanosomes from melanocytes to keratinocytes
- Kojic Acid inhibits tyrosinase, similar to many of the above agents
- Hydroquinone also inhibits tyrosinase; however, unlike the above agents, it is only available through prescription at concentrations above 2%
- Neoglucosamine targets an early step in melanogenesis, specifically inhibiting glycosylation of pro-tyrosinase, and additionally enhances cell turnover
- Retinol combats dark spots by enhancing cell turnover, promoting dispersion of melanin granules, and inhibiting tyrosinase expression
Dr. Rank emphasized that unique formulation challenges accompany each of these ingredients. For example, Vitamin C, the main form of which is L-ascorbic acid, is highly sensitive to light, oxygen, temperature, and pH. Of these, pH is particularly critical because it not only influences the stability but also the efficacy of Vitamin C. At lower pH levels, L-ascorbic acid remains in its non-ionized form, which significantly improves its ability to penetrate the stratum corneum and impart benefits.
Vitamin A Derivatives
While Vitamin A was first discovered in 1910, it wasn’t until the 1990s that the skincare industry made significant advancements in retinol stability, sparking widespread interest in the molecule. Dr. Rank highlighted the multifaceted functions of Vitamin A derivatives, emphasizing their role as powerhouse ingredients. Vitamin A derivatives promote increased keratinocyte proliferation, exfoliate, increase expression of heparin-binding epithelial growth factor (which plays a key role in epidermal repair and regeneration), upregulate transforming growth factor-beta (which promotes synthesis of extracellular matrix components), and downregulate matrix metalloproteinases (which prevents the degradation of extracellular matrix components).
When evaluating Vitamin A formulation, it’s essential to first consider which derivative of Vitamin A is being used in the formulation. Progressing down the Vitamin A metabolism pathway – from retinyl esters to retinol, retinaldehyde, and finally retinoic acid – results in increased potency; however, this comes at the cost of reduced stability and a higher potential for irritation. Irritation potential is an important consideration because it can result in decreased patient compliance and/or patients using reduced product concentrations, which compromises efficacy. For this reason, Dr. Rank concluded by emphasizing the importance of taking solubility, delivery profile, and irritation potential into account when recommending products to patients.
Cleansers
Next, Bechtel took the stage to share valuable insights into the science behind cleanser formulation. Bechtel first reminded us that surfactant-based cleansers are the most common type. Surfactants are surface-active agents with a hydrophobic tail and a hydrophilic head. They are useful in cleansers because the oil-loving tails pick up dirt and oil on the skin, drawing them away from the skin surface, by self-assembling into spherical structures, known as micelles. When the cleanser is rinsed, the micelles are washed away, leaving the skin surface clean.
Although surfactants have undeniable cleansing efficacy, Bechtel explained that some of them can be harsh on the skin and impart dryness and irritation by penetrating the stratum corneum and disrupting the skin barrier structure. Bechtel noted that making a gentle but effective cleanser is a significant area of discussion and innovation. She briefly touched on Neutrogena’s polymer cleansing technology, which addresses this by making micelle structures larger. When thinking about stratum corneum penetration, size matters. Neutrogena’s technology aggregates multiple micelles into one larger structure to prevent stratum corneum penetration and skin barrier disruption.
Bechtel additionally highlighted that pH is another consideration when formulating a gentle cleanser. Cleansers should ideally be in the pH range of the skin, ~4.5-5.5, to further prevent harm to the skin barrier. Altogether, Bechtel stressed that a successful cleanser formulation not only effectively removes bacteria, oil, and dirt but simultaneously preserves the integrity of the skin barrier.
Final Thoughts
Dr. Rank and Bechtel delivered insightful presentations that deepened dermatology residents’ understanding of the science behind skin care product formulation. Their talks were particularly relevant, given how often patients seek guidance from dermatologists on the differences between the plethora of over-the-counter skin care products. They offered practical tips that dermatology residents can bring back to the clinic to help them better differentiate products and ultimately direct patients in selecting the most appropriate options for their individual skin care needs.
About the author
Nikita Menta, BA is a Medical Student at The George Washington University School of Medicine and Health Sciences.
