Rejuvenation through corneotherapy

It was exactly 25 years ago that corneotherapy was first mentioned in a scientific publication¹ and later taken up by other authors^2,3,4. The term was originally coined by the American dermatologist Prof. Albert M. Kligman⁵.
Corneotherapy is based on a very simple principle: if the stratum corneum is healthy, then generally the entire skin and the bodily functions connected to it are also healthy. Conversely, if the stratum corneum is not intact, i.e. if it is damaged, problems with the skin and the body are to be expected.

Good knowledge

What sounds so simple is more complicated in detail, as corneotherapy requires knowledge of the skin structure and its functions – also known as corneobiology⁶ – as well as dermatology and physiological skin care. That is why, in the past, neither the pharmaceutical industry with its topical ointments nor the skin care industry with its creams & other products really concerned themselves with this – after all, the main focus of these preparations was on technical perfection. This can be clearly seen in the formulations of the DAC/NRF (German Drug Codex/New Formulation Formulary)⁷. These are used by pharmacies to manufacture topical preparations, among other things, on site. 
As with cosmetics, physical and microbiological stability and the availability of the active ingredients used are priorities in pharmacy formulations. This is understandable from the point of view of manufacturers and retailers, but as a consequence it is not always in line with the physiological "needs" of the stratum corneum. 

Counterproductive: What is not good for the skin barrier

Excipients play a special role:

• It has long been established that preservatives are not good for the skin flora, also known as the skin microbiome, and, in addition to their allergy potential, also cause resistance.
• High concentrations of paraffins in pharmaceutical preparations lead to the desired absorption of drugs and, in cosmetics, to skin swelling with temporary wrinkle reduction, but from a skin physiology perspective, they also slow down endogenous skin regeneration.
• Emulsifiers serve to stabilise lipophilic active ingredients and fatty substances in an aqueous phase (O/W emulsion) or, conversely, to disperse an aqueous phase with hydrophilic active ingredients in an oil phase (W/O emulsion). When applied to the skin, they perform the same disruptive function, i.e. they emulsify components of the stratum corneum and thus damage its original structure, in particular the lamellar lipid double layers, also known as the bilayer of the skin barrier. What's more, if they are not metabolised in the skin, i.e. if they are not biodegraded, which is mostly the case, they disperse skin components and transport them out of the skin during the next skin cleansing, leaving behind a damaged skin barrier. 

Other excipients commonly used in topical formulations also have adverse physiological effects.⁸

Inside-out

In topical medicinal products for degenerative, inflammatory or microorganism-induced skin diseases, pharmaceutical and cosmetic active ingredients do an excellent job. 
However, the regeneration of the skin barrier usually falls by the wayside due to the excipients. After discontinuing the preparations, recurrence follows after only a short time and a cycle begins. With corticosteroids, which are by far the most commonly used, there is an additional problem: the skin structure changes permanently and becomes more permeable to unwanted guests such as allergens and pathogenic microorganisms. The latter also include those that are part of the skin's own microflora but only thrive under these conditions and become facultative pathogens.  
From the perspective of corneotherapy, the mode of action of the active ingredients in this approach is referred to as "inside-out", i.e. the active ingredient penetrates the epidermis ("inside") and acts there, for example, against the triggers of inflammation. Whether the skin barrier ("out") benefits from this secondarily is desirable, but questionable due to the excipients.

Outside-in

Kligman developed the theory that restoring a damaged stratum corneum alone neutralises many triggers inside ("outside-in") and, above all, prevents them from re-entering from the outside through an intact barrier. Restoring skin moisture using moisturisers was a priority. He sometimes spoke disparagingly of water dermatology, whose effectiveness he was able to prove on the basis of atopic skin. 
The key point was that clinically significant results were achieved with simple substances, such as those used in skin care.
However, compared to an "inside-out" approach, an "outside-in" has the disadvantage that in acute cases, such as inflammation, it only has a preventive effect or, if necessary, only works over a longer period of time – a circumstance that many patients find difficult to accept. However, the advantage of this test of patience is obvious. Ultimately, it is possible to avoid the use of drugs that usually cause side effects.

Optimisation

In a parallel development to corneotherapy, active ingredient-free base creams were developed that are physically and chemically modelled on the skin barrier. They make it possible to replicate the skin barrier in physiological form in addition to skin moisture and to supplement it in the event of damage. 
What initially appeared to be merely an optimisation of Kligman's approach proved to be an advantage in the formulation of active ingredients. The active ingredients can be applied together with a lamellar base cream, which ensures high availability of the active ingredients on the one hand and supports the barrier in a physiological manner on the other. 
It should be mentioned that knowledge about the epidermal barrier has expanded enormously during this time.⁹ The importance of skin moisture and NMF (Natural Moisturising Factor) with regard to free radicals also only became clear elsewhere.¹⁰
Another development that was already in full swing in the 1980s was liposome technology¹¹, which is also based on a lamellar structure, but in this case a spherical one, and mimics natural cell membranes. 
Like human cells, liposomes contain phosphatidylcholine and, due to their related bilayer structure, have the property of fusing particularly easily with the lipid double layers of the skin barrier, making them permeable to active ingredients. 
The increase in permeability is based on the high proportion of chemically bound essential fatty acids in phosphatidylcholine, which is derived from soybean or sunflower oil production. Incidentally, the plant-based exosomes currently in circulation have a similar structure.

Extended corneotherapy

Liposomes have made it possible to open the epidermal barrier for the transport of active ingredients, to enhance their penetration and to close the barrier physiologically again after passage with lamellar creams. This procedure is now known as "extended corneotherapy".¹²
While liposomal preparations tend to contain predominantly hydrophilic active ingredients, phosphatidylcholine-based nanodispersions contain lipophilic active ingredients. The opening principle is analogous and depends solely on the concentration of native phosphatidylcholine.

Anti-ageing

If we assume that preventive anti-ageing is based on the avoidance of dermal damage and the repair of damage on the one hand, and on the high availability of physiological active ingredients on the other, then the contribution of corneotherapy is considerable:

• The skin's own regeneration is not impaired.
• The cooperation between the epidermis and the microbiome remains unaffected.
• Topical preparations contain physiologically compatible compositions.
• Excipients are eliminated and active ingredients are maximally effective at the desired low dosage.
• Topical medicines can be reduced or eliminated altogether during adjuvant corneotherapy, i.e. physiological skin care accompanying the indication.

References

1. Tabata N, O'Goshi K, Zhen YX, Kligman AM, Tagami H, Biophysical assessment of persistent effects of moisturizers after their daily Applications: Evaluation of Corneotherapy, Dermatology 2000 (200), 308-313
2. Lübbe J, Evidence-Based Corneotherapy, Dermatology 2000 (200), 285-286
3. Suvorova K, Korneotherapie der Hautkrankheiten, die von der Störung der Epidermis begleitet werden (in Russisch), Les Nouvelles Esthétiques (Russische Version) 2004 (4), 28
4. Keck C M, Corneotherapie – Pflege und Reparatur der Haut: präzise, effektiv und nachhaltig, J Ästhet Chir 2020 (13), 132–142
5. https://en.wikipedia.org/wiki/Albert_Kligman
6. Kligman A M, Corneobiology and Corneotherapy – a final chapter, International Journal of Cosmetic Science 2011 (33), 197-209
7. https://dacnrf.pharmazeutische-zeitung.de
8. Lautenschläger H, Komplexbildner & Co – ambivalente Ingredienzien in der Kosmetik, Beauty Forum medical 2019 (6), 14-17
9. Lundborg M, Narangifard A, Wennberg CL, Lindahl E, Daneholt B, Norlén L, Human skin barrier structure and function analyzed by cryo-EM and molecular dynamics simulation, J Struct Biol 2018 (203), 149–161
10. Dröge W, Free Radicals in the Physiological Control of Cell Function, Physiol Rev 2002 (82), 47-95
11. Lautenschläger H, Liposomes, Handbook of Cosmetic Science and Technology (Hrsg.: Barel A O, Paye M und Maibach HI), S. 155-163, CRC Press, Boca Raton 2006
12. Lautenschläger H, Corneotherapy – Link between dermatology and cosmetics, Deutscher Apotheker Verlag 2023, ISBN 978-3-7692-8132-3

Dr. Hans Lautenschläger

published in
Beauty Forum
2025 (6), 87-89