There are currently two developments in skin care. On the one hand, there is a move away from skin-damaging additives and the increasing use of physiological ingredients, i.e. substances that are endogenous or metabolised by the body without side effects. On the other hand, special attention is being paid to harmonising the individual substances and the overall compositions with the skin microbiome. Phosphatidylserine – a long-known component from the group of phospholipids – is establishing itself in skin care and fulfils both developments.
Phospholipids
Phospholipids (Figure 1) are essential components of the cell structures of living organisms. They form both the cell-spanning membranes and the intracellular matrix for many metabolic processes. Their proportions in the adult human body are [1]:
- Phosphatidylcholine (PC): 45-55%
- Phosphatidylethanolamine (PE): 15-25%
- Phosphatidylinositol (PI): 10-15%
- Phosphatidylserine (PS): 5-10%
- Phosphatidic acid (PA): 1-2%
Fig. 1: Chemical structures of phospholipids (R1, R2: fatty acid residues)
Phosphatidylserine
Phosphatidylserine (PS) occupies a special position. Its total amount in the body is around 60 g on average. Around half of this is found in the central nervous system alone. Studies indicate an increase in memory and learning performance when taken orally [2, 3] – which is why phosphatidylserine is also offered as a dietary supplement. Higher concentrations are found in cold-water fish such as herring and mackerel [4].
Phosphatidylserine is a component of lecithin, which is a by-product of the extraction of fatty oils from soya, sunflower and other oil plants. Extraction from the lecithin yields PS-enriched fractions, for example products with a phosphatidylserine content of 50-70%; the remainder consists of other phospholipids. Phosphatidylserine from soya is classified by the FDA as GRAS (Generally Recognised As Safe).
In contrast to phosphatidylcholine, the typical building block of liposomes and liquid, biodegradable nanodispersions as well as lamellar cream structures (from hydrogenated phosphatidylcholine) [5], phosphatidylserine is a negatively charged, i.e. anionic phospholipid (Figure 2). In an aqueous environment, in combination with a positively charged oxonium ion (H3O+), it formally has the properties of an acid (Figure 1).
Fig. 2: Anionic character of phosphatidylserine (R1, R2: fatty acid residues)
As with lecithin with its high proportion of anionic phospholipids (PI, PS, PA), no cellular liposomes or lamellar structures analogous to phosphatidylcholine can be formed from phosphatidylserine – with the exception of special compositions [6,7].
The behaviour of phosphatidylserine during programmed cell death (apoptosis) fits into this picture: In this case, phosphatidylserine migrates from its place on the inside of the cell membrane to the cell surface, where it serves as a signal for the macrophages to dissolve and digest the cell in question [8].
Serine
All phospholipids contain long-chain, mostly essential fatty acids (R1-COOH, R2-COOH), which are bound to glycerol in the form of esters (Figure 1) [9]. Among these, linoleic acid (omega-6, double unsaturated) and α-linolenic acid (omega-3, triple unsaturated) and their metabolites play an important role in organisms. Local hormones such as prostaglandins, thromboxanes, prostacyclins and leukotrienes, to name just the most important, are formed from them when ingested orally.
The amino acid serine, which is also bound in phosphatidylserine, plays a central role in the formation of protein structures. Historically, the name serine is associated with silk production. During the processing of raw silk, the so-called sericin, in which serine is abundant, is removed.
In addition to its occurrence in proteins such as collagen, serine is also found in the catalytically active centre of special proteases, i.e. enzymes that break down proteins. These serine proteases include trypsin (digestion) and thrombin (blood clotting).
Mediator
On the one hand, phosphatidylserine activates the macrophages as described, on the other hand, inflammation-triggering messenger substances such as cytokines are suppressed during this process and TGF-ß (transforming growth factor) and prostaglandin E2 are formed [10]. Phosphatidylserine is also increasingly present on the cell surfaces of external injuries and activates coagulation and the healing process. The anti-inflammatory effect can be demonstrated in vivo using rat paw oedema [11].
Skin smoothing
While liposomes and phosphatidylcholine-based nanodispersions spontaneously fuse with the lipid bilayers of the skin barrier, lower its phase transition temperature and thus facilitate the penetration and possibly also the permeation of active ingredients carried along, aqueous, biodegradable nanodispersions with phosphatidylserine adhere to the outer skin surface. Phosphatidylserine behaves similarly on artificial skin [12].
The production of stable PS dispersions is practically only possible in combination with a comparatively high concentration of phosphatidylcholine. The resulting lotions can be easily spread like water and are particularly suitable for the care of erythematous, eczematous and atopic skin. The affinity of phosphatidylserine to the corneocyte surfaces results in long-lasting skin smoothing.
Support for the skin barrier
The critical micelle formation concentration (CMC), e.g. of didecanoylphosphatidylserine, is 0.096 mM [13] and identifies phosphatidylserine as an anionic emulsifier. After their use in skin care creams, anionic emulsifiers usually have a wash-out effect, i.e. when the skin is subsequently cleansed, the emulsifiers are reactivated by water and use this opportunity to transport lipids and barrier substances out of the skin. This negative effect of synthetic anionic emulsifiers is completely absent in phosphatidylserine.
Like phosphatidylcholine, the essential fatty acids of phosphatidylserine form anti-inflammatory metabolites by being split off by the phospholipases A1 and A2 and oxidised in the skin by 15-lipoxygenase (15-LOX). The linoleic acid components of phosphatidylserine and phosphatidylcholine also form a substrate for the linoleic acid-containing ceramide I (aka ceramide EOS) and thus support the barrier function of the lipid bilayers, stabilise transepidermal water loss (TEWL) at a physiological level and contribute to the moisture retention capacity of the stratum corneum. All in all, this results in a pronounced regenerative effect.
Emulsions
Oil-in-water emulsions (O/W) are expected from an anionic emulsifier. However, the geometric arrangement of the charge carriers in the phosphatidylserine molecule leads to water-in-oil emulsions (W/O), which generally leave a richer feeling on the skin – further enhanced by the aforementioned surface adhesion. However, phosphatidylserine emulsions are less easy to stabilise – if one wants to completely avoid additional additives in a physiological composition. For this reason, the biodegradable nanodispersions mentioned above, which contain phosphatidylserine and phosphatidylcholine together with lipid and active ingredients, are more commonly used in practice. They are characterised by small particle sizes and high water content.
Oleogels
An alternative to aqueous nanodispersions are anhydrous oleogels, also known as lipogels. Physiological, biodegradable oleogels are based on triglycerides, waxes and structure-forming components that are also found in the lipid bilayers of the skin barrier – such as long-chain fatty acids, cholesterol or its related phytosterols (contained in shea butter, for example) [14]. The anionic character of phosphatidylserine naturally plays no role in oleogels. Cosmetic and/or pharmaceutical compositions are possible which can be adjusted to practically any skin condition or medical indication. As with liposomes and nanodispersions, phosphatidylcholine is added as a penetration enhancer.
The lack of a water phase in oleogels makes many counterproductive components such as preservatives, emulsifiers (aka surfactants), complexing agents and alcohols (solvents) superfluous. It is in the nature of phosphatidylserine and phosphatidylcholine to stabilise polar and hydrophilic active ingredients – such as urea – in the lipophilic matrix to a certain degree. Higher concentrations can be achieved by micronised active ingredients, particularly in pharmaceutical preparations.
With oleogels, the superficial concentration of water-soluble ingredients is eliminated when the water contained in the emulsions evaporates on the skin. The resulting hypertonic conditions are known to cause temporary but harmless irritation (redness, burning), especially with O/W emulsions and sensitive skin. A decisive advantage of oleogels for topical medical preparations is the high physical and chemical stability required for pharmaceuticals in the production of viscous to semi-solid preparations, including ointments and suppositories. Nanoscale cochleates, which are tubular structures formed from phosphatidylserine and calcium ions, are also suitable carriers for medicinal products [15].
Microbiome compatibility
While conventional oleogels made from paraffins are permanently occlusive, oleogels containing triglycerides and phospholipids are at best temporarily occlusive. There is a simple reason for this. Just like the epidermis, the dermal microbiome is equipped with representatives of all enzyme classes in its diversity and is capable of many biochemical reactions: [16]
- Oxidoreductases carry out oxidations and reductions.
- Transferases transfer functional groups from one substance to another. Among other things, they are involved in the breakdown of fatty acids through β-oxidation.
- Hydrolases break down molecules with water, e.g. triglycerides into glycerol and acids.
- Lyases cleave bonds or entire molecules.
- Isomerases change the steric structure of molecules.
- Ligases link two molecules together.
The enzymes even allow the degradation of larger molecules. This also applies to triglycerides and native phosphatidylserine (> 800 Dalton). As the microbiome is adapted to the epidermis, counterproductive disturbances are largely avoided by using physiologically degradable components in skin care products and ointments – provided that the concentrations are also within a tolerable range. For example, very high concentrations of antioxidants such as ascorbic acid (vitamin C) tend to be counterproductive for the microbiome, as the oxidation and formation of fatty acids, which is important for the acid mantle, is hindered.
Phosphatidylserine and the oleogels produced with it fulfil the conditions of microbiome compatibility, while pharmaceutical oleogels and base creams based on paraffins promote the growth of populations of anaerobic microorganisms due to their long-lasting occlusive effect, which lead to an increased susceptibility to inflammation and recurrences in cases of perioral dermatitis or rosacea, for example.
Applications
Oleogels should be used sparingly as the concentration of lipids is around 3-4 times higher than that of the O/W emulsions most commonly used – a fact that is usually unfamiliar to users in their daily skin care routine. Phosphatidylserine oleogels are also well suited for massages due to the skin smoothing effect described above. With regard to other diverse properties of phosphatidylserine not listed here, reference should be made at this point to the overview in a dissertation from the University of Halle. [17]
Conclusion
As in the food sector, there are various trends in skincare that emphasise the origin of the individual components. Positive terms such as natural cosmetics, organic cosmetics and biodegradability on the one hand and synthetic ("chemical") ingredients on the other play a role. Apart from the fact that advertising is often incorrect and emphasises one or other aspect in particular, for example the additives used in the products are hardly mentioned at all and nature, like the chemical industry, is known to contain many substances that have an allergic or irritant effect, these terms miss the point of skin care.
For sustainable skin care, it is essential that a good skin condition is achieved through its use, but that there are no long-term side effects. The origin of the substances used is irrelevant. Physiological compatibility is the most important criterion, i.e. the ingredients as a whole fit seamlessly into the biochemical relationships of the skin and microbiome. Phosphatidylserine is a component that fulfils these requirements.
Terms and abbreviations
Atopic skin – Sensitive skin that repeatedly reacts to various endogenous and exogenous factors in phases with redness, scaling, itching or inflammation – often referred to synonymously as neurodermatitis or atopic eczema.
Ceramides – are a diverse family of amides that result from the acylation of the aminoalcohol sphingosine with long-chain, partly functionalised fatty acids. Together with cholesterol and long-chain fatty acids such as palmitic acid, ceramide I forms the lipid bilayers of the skin barrier.
CMC – The CMC indicates the concentration of a substance in water above which agglomerates are formed in the form of micelles. Due to the symmetrical arrangement of the charge distribution, they usually have a spherical shape. If the charges and the geometry of the molecules allow it, liposomes and lamellar structures can also form, as with phosphatidylcholine.
Eczema – Inflammatory skin reaction, usually triggered by external (work) substances with allergenic or irritant effects. Often chronic, for example due to repeated contact with aqueous media that contain small amounts of detergents (washing-up liquid) and damage the skin barrier in the long term.
Erythema – skin irritations of various origins that cause reddening of the skin. Example: sun erythema
Excipients that are harmful to the skin – Emulsifiers, consistency agents, preservatives, antioxidants, complexing agents, fragrances, dyes and pigments are used as excipients in skin care products. Preservatives and many fragrance components are characterised by allergenic or irritating properties. Non-biodegradable oil-in-water emulsifiers (O/W) cause skin barrier substances to be washed out during skin cleansing. Antioxidants and complexing agents influence the oxidoreductases of the dermal microbiome and the epidermis.
Corneocytes – is the name for the horny cells on the surface of the skin. They are part of the outer skin barrier (stratum corneum).
Lecithin – The crude oil produced during the extraction of oilseeds contains phospholipids, glycolipids, sterols, free fatty acids and carbohydrates, which are separated and dried as an aqueous sludge (crude lecithin) that also contains triglycerides. Pure lecithin in the form of brown-yellow granules is obtained from the crude lecithin by deoiling and further purification processes. The vast majority of lecithin comes from the production of soya oil and is further processed as a food emulsifier. A small amount is obtained from chicken eggs (egg lecithin); the phospholipids of egg lecithin differ from plant phospholipids in terms of their fatty acid bound to glycerol.
Liposomes – are physically and chemically similar to the cells of living organisms in terms of their size and the structure of their double-layered membranes (bilayers).
Occlusivity – occlusive skin care products or topical medicines form a superficial film on the skin that is impermeable to water vapour and oxygen and in this respect has properties comparable to a medical adhesive tape (plaster).
Rat paw oedema – This is an in vivo test in which inflammation is provoked by injecting carrageenan or other substances into the rat paw [18].
TEWL – transepidermal water loss.
Summary
The availability, effect and tolerability of ingredients in cosmetic products and topical pharmaceutical preparations reflect the co-operation between the epidermis and the skin's microbiome. Physiological components in appropriate dosages therefore offer the best prerequisite for side-effect-free (long-term) applications.
Water-containing skin care products, including oil-in-water (O/W) and water-in-oil (W/O) emulsions, require excipients to ensure the microbiological, physical and chemical stability of the products. Excipients affect both the skin and the microbiome.
Anhydrous oleogels made from physiologically compatible and biodegradable components are largely free of additives. Phosphatidylserine, a physiological component of plant and human cell membranes, is suitable for microbiome-compatible cosmetic and indication-accompanying skin care.
Literature
[1] P. van Hoogevest, Phospholipids – Properties, manufacturing and use, 5th International Symposium on Phospholipids in Pharmaceutical Research, Heidelberg 2017.
[2] H-Y. Kim, B. X. Huang and A. A. Spector, Phosphatidylserine in the Brain: Metabolism and Function, Progress in Lipid Research 2014, 56, 1-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258547/, accessed 6 July 2023.
[3] H. Dannert, Einfluss von Phosphatidylserin auf den durch Glycolipidtransferprotein katalysierten Gluco- und Galactocerebrosidtransfer zwischen Liposomen, Dissertation Eberhard-Karls-Universität Tübingen 2005, p. 11-14. https://bibliographie.uni-tuebingen.de/xmlui/bitstream/handle/10900/44743/pdf/Doktorarbeit_Hans_8112005_Druckversion.pdf?sequence=1, retrieved on 6.7.2023.
[4] S. W. Souci, E. Fachmann and H. Kraut, Food Composition and Nutrition Tables, Medpharm Scientific Publishers Stuttgart 2008.
[5] H. Lautenschläger, Cosmeceuticals – Phospholipids, medical Beauty Forum 2018, 2, 14-18.
[6] M. Babincová and E. Machová, Dextran Enhances Calcium-Induced Aggregation of Phosphatidylserine Liposomes: Possible Implications for Exocytosis, Physiol. Res. 1999, 48, 319-321.
[7] F. Miere et al, Preparation and Characterisation of Two Different Liposomal Formulations with Bioactive Natural Extract for Multiple Applications, Processes 2021, 9, 432 (https://doi.org/10.3390/pr9030432).
[8] R. B. Birge et al, Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer, Cell Death and Differentiation 2016, 23, 962-978.
[9] Phosphatidylserine isolated from soya contains approx. 60% polyunsaturated fatty acids, approx. 20% monounsaturated and approx. 20% saturated fatty acids (data sheet PS P 70 dated 17 August 2015, Lipoid GmbH, Frigenstr. 4, D-67065 Ludwigshafen).
[10] P. M. Henson and D. L. Bratton, Antiinflammatory effects of apoptotic cells, The Journal of Clinical Investigation 2013, 123, 2773-2774.
[11] K. Mäder, M. Klein, S. Mauch, G. Ramos, U. Hofmann and A. Meister, Phosphatidylserine enriched phospholipids as anti-inflammatory agents, 5th International Symposium on Phospholipids in Pharmaceutical Research, Heidelberg 2017.
[12] S Zellmer, D Reissig and J Lasch, Reconstructed human skin as model for liposome-skin interaction, J Control Release 1998, 55, 271-279.
[13] Reproducible CMC values are only available for synthetic phosphatidylserine. The native phosphatidylserine obtained from lecithin varies in terms of the fatty acid composition and may also contain admixtures of other phospholipids. The value of didecanoylphosphatidylserine comes from Avanti polar Lipids, https://avantilipids.com/tech-support/physical-properties/cmcs, retrieved: 8.12.2022.
[14] H. Lautenschläger, Vorteile von Produkten ohne Wasser und Hilfsstoffe, Kosmetik International 2017, 6, 56-58.
[15] A. Lipa-Castro, F. X. Legrand and G. Barratt, Cochleate Drug Delivery systems: An Approach to their Characterisation. International Journal of Pharmaceutics 2021, 610, 121225 (https://doi.org/10.1016/j.ijpharm.2021.121225).
[16] H. Lautenschläger, Cooperation is everything – cosmetics and the skin microbiome, Medical by Beauty Forum 2022, 6, 8-11. Kooperation ist alles – Kosmetika und Hautmikrobiom
[17] M. E. Klein, Phosphatidylserin- (PS) und Phosphatidylglycerol- (PG) angereicherte nanoskalige Formulierungen als antiinflammatorische Agentien: Herstellung und umfassende Charakterisierung. Dissertation Martin Luther University Halle-Wittenberg 8 April 2021.
[18] N. Shejawal, S. Menon and S. Shailajan, A simple, sensitive and accurate method for rat paw volume measurement and its expediency in preclinical animal studies, Human & Experimental Toxicology 2014, 33 (2), 123-129.
Translated from: Hans Lautenschläger, Trend zu physiologischen Inhaltsstoffen – Phosphatidylserin in der Hautpflege, Chemie in unserer Zeit 2024, 58 (2), 93-97. Copyright © 2023 Wiley-VCH GmbH. Reproduced with permission. Final version: https://doi.org/10.1002/ciuz.202300005; first published: 11. August 2023.
|
Menu publications
>>
special actives
