Lamellar compositions in topical dermatological and cosmetic preparations

The first cell-like life forms emerged in the primordial oceans. Over millions of years, these evolved into multicellular organisms which, in addition to their cell-like internal structure, developed complex organs and circulatory systems, which in turn contain functional compartments – enclosed by membranes – that perform a wide variety of tasks.

Cell membranes

What all these organisms have in common is that their membranes contain phospholipids, alongside other substances responsible for transport from the inside to the outside and vice versa. These phospholipids enable the membrane structures. A typical feature is their bilayer structure, with phosphatidylcholine being the most abundant component.

Fig.: Cross-section of a cell membrane¹

Liposomes

Artificial replicas of cells containing phosphatidylcholine held a special fascination from very early on. They were first described in 1964² and were given the name ‘liposomes’ in 1968.³ It did not take long for the first ideas to emerge regarding the use of these structures, which are similar in size to human cells and have a physiologically compatible composition, as carriers for drugs, particularly in the field of cancer treatment. The widespread use of intravenous applications ultimately failed later on because the liposomes, in their original compositions, exhibited a certain degree of physical instability and the phosphatidylcholine they contained had limited chemical stability⁴. Another important issue was preservation. Vegetable lecithin and the phosphatidylcholine derived from it inactivate more or less all preservatives⁵, apart from the fact that the fatty acid composition (linoleic acid, alpha- linolenic acid and saturated long-chain fatty acids) varies to some extent depending on origin and season. 
Furthermore, when administered systemically, liposomes tend to fuse with other compartments along their path before reaching their destination. However, they have been used in medicinal applications, for example with the antifungals econazole (Pevaryl^® topically) and amphotericin B (intravenously)⁶.

Drug delivery

However, these properties of liposomes did not prevent their use in cosmetics, and so a typical hype arose in the cosmetics industry⁷, which, as usual, lasted only a few years but was underpinned by continuous further development of these systems that continues to this day. They were significant for the skin from the outset, as liposome bilayers can fuse with the analogous lipid bilayer structure of the skin barrier. This process significantly facilitates the transport of hydrophilic active ingredients, in particular, through the skin barrier. In other words: liposomes are a physiological penetration enhancer (carrier) par excellence.⁸

Exosomes

Similar to liposomes, liquid nanoparticles of the same size with a single-layer phosphatidylcholine membrane function in the same way. They enable the transport of lipophilic active ingredients through the skin barrier.⁹ 
Also similar to liposomes are the smaller exosomes.¹⁰ These are spherical cell components with membranes made of phosphatidylcholine, which are released (exocytosis) as required and delivered to the cell’s surroundings. Exosomes have transport and messenger functions, as they contain bioactive signalling molecules that communicate with other cells. The plant-derived exosomes found in cosmetics occur, for example, in cold-pressed plant juices.
Animal and human exosomes are isolated from bodily fluids (e.g. blood), tissue, and a wide variety of cells (e.g. platelets), processed and used in aesthetic medicine. Applications administered topically or via injection aid skin regeneration and are used to combat skin ageing, inflammation, hair loss and hyperpigmentation.

Lamellar gels

Quietly, another development was taking place, which began in 1979 with a doctoral thesis bearing the unspectacular (translated) title ‘Production and Stabilisation of Emulsions Using Lecithin’. This work demonstrated how planar (lamellar) lipid bilayers can be produced in water from hydrogenated phosphatidylcholine (PC-H). With the aid of ultrasound or, for the first time, a high-pressure homogeniser, stable lamellar gel phases could be produced.¹¹ This cannot be achieved with standard stirring equipment; only unstable dispersions result.
Like unsaturated phosphatidylcholine, PC-H is a physiological building block, but with a fatty acid composition consisting of long-chain, exclusively saturated fatty acids. 

Lamellar skin barrier

Electron microscope images later showed that the resulting structure corresponded exactly to the physical structure of the skin barrier with its planar lipid bilayers¹², whose composition consists of a molar ratio of ceramides/cholesterol/long-chain fatty acids of 1 : 0.9 : 0.4.¹³ Later, the initially pure PC-H gels were additionally enriched with skin barrier components or analogous substances such as sterols and ceramides, thereby coming ever closer to the composition and biochemical properties of the lamellar skin barrier. At the same time, originally protected designations have evolved into technical terms. One example is Derma Membrane Structure (abbreviation: DMS), which in this context is sometimes also referred to as skin-identical or biomimetic. To date, the lamellar components have proven to be highly variable in terms of their composition of fatty acids, sterols, waxes, oils, ceramides and their respective dosages. 
However, the incorporation of ceramides can be a critical issue due to their poor solubility. A hallmark of quality in lamellar base products is therefore the absence of microcrystalline ceramide residues in concentrates, which become visible under a polarising microscope. Diluted products manufactured from concentrates contain additional thickening agents such as hydroxyethylcellulose. 

Physiological skin protection

Lamellar products are highly versatile. Naturally, occupational skin protection is of particular interest.¹⁴ Lamellar formulations have contributed to a move away from protective products containing emulsifiers and paraffin¹⁵ and are used, for example, as an emergency solution when conventional systems reach their limits in everyday working life and are not effective enough.^16,17 
On the other hand, the simultaneous use of PC-H and phosphatidylcholine enables the creation of lamellar gel preparations that are used for problem skin.¹⁸ 

Microstructure of the skin barrier

The intact lamellar structure of the skin barrier is arranged in an orthorhombic closest-packed configuration. In disorders such as atopic skin, a less dense hexagonal packing predominates. The packings and their transitions have been intensively studied in recent years¹⁹ and depend on skin temperature, the individual composition of the bilayers, and their local position within the layers of the skin barrier.
Orthorhombic closest-packed arrangements are frequently found in lipids with a uniform structure, which are used as components in skincare products.²⁰ It is therefore not entirely correct to assume a priori that a particular layer arrangement is associated with particularly high stability or low permeability, as the chemical structure and its solubility behaviour upon contact with other substances play a decisive role. 
The situation becomes even more complex in multi-component systems such as the skin barrier. When exposed to surfactant solutions, such as those used for skin cleansing, the ceramides in the skin barrier prove to be the most resistant and are the last to be removed. Consequently, the orthorhombic packing of a lamellar skincare product is neither a unique technical feature²¹ nor a guarantee of a particularly high protection factor,²² particularly when the properties are compared not with lamellar products but with a placebo, i.e. a conventional emulsion.²³ A study using uniformly structured model phospholipids such as dipalmitoylphosphatidylcholine (DPPC) and distearylphosphatidylcholine (DSPC)²⁴ gives an idea of just how complex the reality²⁵ is. 
Comparisons of lamellar compositions with one another are scarce. However, the complexity and various factors influencing the packing have already been described in detail previously.¹¹
In production, lamellar concentrates are processed into end products with additional active ingredients and excipients for subsequent applications. Measurements of the packing density of these multi-component systems, as ultimately applied, are generally not available.
It goes without saying that penetration enhancers, such as oleic acid, lead to changes in the skin barrier packing. This applies in particular to liposomes. The processes taking place in the barrier can be tracked very effectively via the temporal course of transepidermal water loss (TEWL). It is only natural to use these physiological or physiologically compatible penetration enhancers in dermatology and cosmetics wherever possible. 
With phosphatidylcholine-based liposomes, it can be observed that the increased TEWL following application normalises after a few hours. This normalisation can be accelerated by the immediate subsequent application of lamellar PC-H preparations. In the corneotherapy established by A. M. Kligman²⁶, this procedure is also referred to as extended corneotherapy.²⁷  

Lipid components of lamellar formulations

In addition to plant oils with low packing densities, butter-like substances such as shea butter or waxes such as carnauba wax are used in lamellar formulations, as well as squalane (a hydrocarbon; the hydrogenated form of sebum squalene) and synthetic esters (oils) such as isostearyl isostearate. Ultimately, there is a vast array of combinations that can be tailored to individual skin types. 
For skin prone to acne and blemishes, one tends to use plant oils which, due to their content of essential fatty acids and their role as a substrate for epidermal 15-lipoxygenase (15-LOX), form anti-inflammatory metabolites, whilst for skin protection, waxes or triglycerides of saturated acids such as trihydroxystearin are used. In products for atopic skin, plant oils containing gamma-linolenic acid, such as borage or evening primrose oil, can be a useful addition; they compensate for any existing deficiency in delta-6-desaturase. 
With lipid phases consisting of several components, barrier-repairing (regenerative), skin-protecting and anti-inflammatory properties can be adjusted proportionally. 

Efficacy

Not only in emulsions, but now also in lamellar – also known as multilamellar or ortholamellar – products, benefits such as regeneration, relief, and the reduction of inflammation and redness are highlighted, some of which are not covered by the Cosmetics Regulation (KVO). In some cases, these are associated with the lamellar structures, although on closer inspection, questionable additives such as 4-tert-butylcyclohexanol are also used, which is to be classified in the same way as Laureth-9 (INN: Polidocanol).²⁸ However, this does not rule out the support of the endogenous regeneration of the skin barrier through the presence of exogenous lamellar structures (without additives).²²

Pharmacy formulations

Given the advantages of physiological lamellar products, it is to be hoped that they will be incorporated into the NRF formulations²⁹ of the magistral compounding departments of pharmacies for therapeutic purposes.³⁰ This is because many pharmaceutical formulations are still being introduced in this field that contain barrier-damaging emulsifiers, allergenic preservatives and occlusive paraffins that inhibit regeneration. 
Lamellar products without counterproductive additives are particularly suitable for dermatological skincare in children.³¹
The Ziegler Formulation Library now includes at least one preservative-free lamellar base cream.³² It does not contain ceramides, as compounds in this class are not yet listed in the European Pharmacopoeia (Ph. Eur.)³³. PC-H is also not included in the Ph. Eur., but an equivalent Drug Master File (DMF) exists.³⁴ 
The lamellar base creams can be used in both dermatology and cosmetics and significantly facilitate compliance as well as the transition between dermatological therapy and cosmetic prevention. Individual adjustments are possible through modular components, as lamellar base creams can be easily adapted by stirring in liquid lipids and aqueous active ingredient solutions.³⁵
Another consideration when formulating lamellar base creams for regenerative purposes is the fact that endogenously controlled regenerative processes vary from person to person. Specifically, lipids, free fatty acids, sterols and ceramides are synthesised more quickly, more slowly or in varying quantities when the skin barrier is compromised.³⁶

Outlook

A further development involves the use of skin barrier-analogue components, including hydrogenated phosphatidylcholine, in paraffin-free, anhydrous oleogels.³⁷ These offer the advantage of eliminating the need for glycols and polyglycols currently still used in lamellar formulations, such as pentylene glycol, hexylene glycol and glycerine. The phospholipid content in the form of PC-H, but where appropriate also PC, allows for combination with polar, water-soluble cosmetic and pharmaceutical active ingredients. The oleogels are microbiome-compatible, biodegradable and do not require any additional excipients typical of water-based products, such as thickeners, complexing agents and preservatives. 
Nothing is currently known about the packing densities of this product class in relation to their specific composition and corresponding comparisons with the skin barrier.

References

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Dr Hans Lautenschläger

published in
Diskurs Dermatologie
2026 (3), 16-19