It seems like everyone in skincare talks about new innovation. In the race to stay relevant and at the top of consumer’s minds, companies aim to create a sense of freshness or even FOMO. But, is the rate of innovation really that rapid in skincare? Or, are companies just repackaging the same things under a new name?
Multiple areas within skincare are primed for innovation. Be it discovery of new ingredients, or incremental refinement of already known ingredients. New delivery systems to better get the actives to the places in the skin where they need to exert their effect. Novel compositions of already known ingredients that have new synergistic effects, or a specifically tailored to a specific type of skin issue, etc. Below I will just give a handful of examples.
Fresh or stale
To give an idea of the rate of innovation I will give a few examples of what is considered relatively new innovations in skincare. Specifically around ingredients and delivery systems.
At an ingredient level the rate of innovation might not be as rapid as advertised. Take for instance AlphaRet, ethyl lactyl retinoate, a conjugate between AHA and retinol. This compound was tested back in 2015 [1] with a prior patent of the compound in 2014 [2]. While much more recent than retinol (first used in 1943 for treatment of acne), it is soon a decade old. Another example would be malassezin which is being more heavily marketed as today’s discovery which was first described in 2001 [3]. The article states the mode of action, an arylhydrocarbon receptor (ACR) agonist, that leads to inhibition of melanin production.
Similarly, across delivery systems. Various micellar and liposomal systems have a long and rich research history (as has other delivery systems). For instance, micellar systems that react to a series of external stimuli such as pH, specific wavelengths of light or similar has a long research history [4]. Take the example of active release of compounds based on the presence of free radicals, this dates back to 2010 [5]. Today, there are multiple off the shelf time release, targeted release, etc liposome systems that can be used for specific delivery purposes.
The fact is that the basic research needed to develop new ingredients and new delivery technologies takes time, and does not accommodate the skincare industry’s demand for newness. This creates situations where incremental gains are oversold.
This overselling or promising claims language is further amplified by the consumer demand for better and more efficacious products. Today, up to 71% of consumers say their needs are not being met. However, presenting decade-old research as the latest groundbreaking discovery is a disservice to consumers, and likely also a driving force behind the dissatisfaction felt as expectations are much higher than what can feasibly be delivered.
With this hunt for more efficacious treatments, there is a blurring of the lines between cosmetics and pharmaceuticals, aptly called cosmeceuticals [6]. So maybe the way to increase the rate of innovation is to take cues from pharmaceutical drug development. Below I highlight a few though experiments that can take us in that direction.
Rapid discovery of new cosmetic ingredients
Many of the current cosmetic ingredients are derived from plants, and based on learnings from traditional medicine. Most of these extracts are from terrestrial plants, leaving a lot of marine species untapped which Sirenas is currently exploring in the more traditional human health space. However, we have little or no knowledge about how these newly discovered compounds might work. To rapidly shift through thousands or even millions of candidate compounds we have to automate the process. An interesting and promising approach is to combine phenotypic assays with imaging and neural networks, similar to what is done by Recursion. In short, if we are looking for a compound promoting cell differentiation of keratinocytes, we already have compounds that do this, and if we treat keratinocytes with those and observe how the cells change structure, even record it in a series of images at specific timepoints we now have a “phenotypic fingerprint”. Now when treating the keratinocytes with an unknown compound, if we observe the same pattern of structural change over time there is a high likelihood that this compound has a similar effect (promoting cell differentiation). The problem of identifying compounds with a specific effect now boils down to “fingerprint matching” with an already known compound. This problem can be automated using neural networks specifically trained to find similarity between the image series, either directly or in a more abstract form by comparing the latent space of images.
While the above will speed up the discovery process, there are still safety testing and further characteristics of the compound to map out, so this is by no means a silver bullet. The transition from in vitro lab research to consumer grade and safe product will still take time, but we have the ability to significantly reduce discovery time, and take a more systematic approach to finding new actives with desired mechanisms of action.
Borrowing from precision medicine
Precision medicine is the concept that if we have the ability to identify the root cause of a given issue (a set of specific driver mutations in cancer) we can tailor the treatment to target this root cause, and have better and more efficacious outcomes. And that this better outcome can be achieved with already existing tools, actives etc.
This then presents another approach to skincare innovation, where it is not new development of “primary” technology in the form of ingredients and novel delivery systems, but in getting better utilization of already available ingredients.
The core tenant of precision medicine is the right drug, to the right patient, at the right time. As skin is highly dynamic, adjusting to both internal and external stimuli, have particular predispositions based on ethnicity and genetics, lifestyle etc. we end up in a situation each persons skin is unique. This presents a challenge for the current mass market skincare brands, and have led to the development various degrees of personalized skincare. An ideal solution to a truly personalized skincare treatment would involve solving the following challenges:
- Diagnose the root cause of the consumers skincare issues, ideally down to a biological pathway level
- Obtain, in a compatible vehicle, efficacious active ingredients against each of the possible pathways to create unique treatments for each consumer
- Be able to produce and deliver these unique treatments at scale
- Track the progress of the treatment with each consumer to adjust treatment with subsequent changes in skincare issues, or resolution of issues
This would allow for a treatment regimen to adapt to the changing nature of each consumers skin, and thereby deliver the most optimal set of ingredients at any given time. Integrating the real world consumer outcomes into a learning model could lead to better recommendations for both current and future consumers further driving a more performant treatment.
Reducing the above theoretical model to practice have multiple additional challenges. Two of the most obvious would be: 1) the frequency of treatment changes relative to measured effect of treatment. It might be that the skin is actually adapting to external stimuli faster than the treatment effect, leading to endless lag in the recommendations. 2) Confounding factors may limit the feasibility of ingredient prediction, meaning that lifestyle choices and other external factors may have a larger effect size on skin health than that of treatment.
This area of tailored treatments is relatively new in skincare, but have received a lot of attention in the healthcare space from companies like Tempus, Flatiron, and also major established players like Pfizer. All based on the fact that we can create better outcomes if our treatment is specific rather than generic.
Probiotics and our microbiome
Our skin is a ecological niche to a rich and diverse microbiota that through a complex interaction with each other and us as a host confer multiple beneficial effects. The molecules excreted by our microbiome is becoming more and more interesting from a commercial and therapeutic perspective. For instance, specific bacterial-derived peptides have a similar effect as antibiotics, and are used by the bacteria to inhibit the growth of other adjacent organisms. This can be exploited to clear out specific pathogenic organisms, while leaving the rest of the natural flora untouched, as opposed to antibiotics which is a major disruptor of the microbiome. Specific skin native viruses have been successfully deployed in the reduction of C. acnes in phase I clinical trials.
More and more evidence show that there is a correlation between skin microbiota composition and biophysical skin properties. In example, Streptococcus abundance increase until puberty and is associated with higher skin elasticity. In vitro experiments show that treating human fibroblasts with the supernatant from a facial skin swap from younger individuals increased gene expression of collagen, filaggrin and lipid synthesis proteins [7].
Lactobacillus has also been explored, and is correlated with reduced photo-aging, and has been shown to aid in the integrity of the skin barrier via increasing expression of skin-junction proteins.
A huge obstacle to the commercialization of these correlative studies is isolation of the effector molecules. For meaningful scale we need to be able synthesize the effector molecules. Another approach would be to grow the microorganism in a controlled environment, which is also proving challenging for a majority of cases due to the complex interaction with the host and other microorganisms. To the extreme that researchers are building small “organs on a chip” to study the interactions [8].
It is clear that our own skin is a potential treasure trove of potential therapeutic solutions, and exploiting the extensive co-evolution between us and our microbiome is an exciting near future reality. For a more extensive review of some of the potentials the readers should refer to Nicholas-Haizelden et al. 2023 [9].
Many more areas of innovation
In this post I have touched on a few areas of potential innovation in skincare, but there are many more. Personally I am really excited about the recent progress in our ability to better understanding skin penetration of compounds via different imaging technologies. This has the potential to help us create better formulations, and drive more actives into the right parts of the skin. Likewise, our ability to diagnose skin issues is continuously evolving thanks to advances in image analysis based on deep neural networks, and at the same time new imaging modalities are being miniaturized and reaching cost efficiencies that allows them to become consumer-facing devices. Figuring out how such knowledge and tools can be used to create amazing consumer experiences will allow for insights into skin biology at population-level scales which has not been possible before.
In future posts I will return to both imaging, image analysis and skin penetration and what promises these areas of development might hold for our understanding of skin biology.
References:
[1] Katz, Bruce E., Joseph Lewis, Laura McHugh, Arthur Pellegrino, and Lavinia Popescu. “The tolerability and efficacy of a three-product anti-aging treatment regimen in subjects with moderate-to-severe photodamage.” The Journal of Clinical and Aesthetic Dermatology 8, no. 10 (2015): 21.
[2] https://patents.google.com/patent/WO2015073769A1/en
[3] Wille, Gregor, Peter Mayser, Wiebke Thoma, Thomas Monsees, Annette Baumgart, Hans-Joachim Schmitz, Dieter Schrenk, Kurt Polborn, and Wolfgang Steglich. “Malassezin — a novel agonist of the arylhydrocarbon receptor from the yeast Malassezia furfur.” Bioorganic & medicinal chemistry 9, no. 4 (2001): 955–960.
[4] Saravanakumar, Gurusamy, Jihoon Kim, and Won Jong Kim. “Reactive‐oxygen‐species‐responsive drug delivery systems: promises and challenges.” Advanced Science 4, no. 1 (2017): 1600124.
[5] Ma, Ning, Ying Li, Huaping Xu, Zhiqiang Wang, and Xi Zhang. “Dual redox responsive assemblies formed from diselenide block copolymers.” Journal of the American Chemical Society 132, no. 2 (2010): 442–443.
[6] Pandey, Amarendra, Gurpoonam K. Jatana, and Sidharth Sonthalia. “Cosmeceuticals.” (2019).
[7] Kim, Gihyeon, Misun Kim, Minji Kim, Changho Park, Youngmin Yoon, Doo-Hyeon Lim, Hyeonju Yeo et al. “Spermidine-induced recovery of human dermal structure and barrier function by skin microbiome.” Communications Biology 4, no. 1 (2021): 231.
[8] Jalili-Firoozinezhad, Sasan, Francesca S. Gazzaniga, Elizabeth L. Calamari, Diogo M. Camacho, Cicely W. Fadel, Amir Bein, Ben Swenor et al. “A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip.” Nature biomedical engineering 3, no. 7 (2019): 520–531.
[9] Nicholas-Haizelden, Keir, Barry Murphy, Michael Hoptroff, and Malcolm J. Horsburgh. “Bioprospecting the Skin Microbiome: Advances in Therapeutics and Personal Care Products.” Microorganisms 11, no. 8 (2023): 1899.