The technique of micro-encapsulation by homogenisation into a lipophilic vehicle constituted by lecithin has been recently used by Sinerga Research Centre to obtain a matrix of phospolipids/water/ carbohydrates into which particular and highly effective lipids are incorporated that are also able to spontaneously form nanoparticles when dispersed in water. This paper discusses the use of a cosmetic raw material containing a combination of hydrophilic and lipophilic substances in the same product; reproducing the skin’s composition. In fact, key lipid classes (cholesterol, ceramides, and phospholipids) are associated by encapsulation with a hydrophilic (trehalose) or lipophilic (ethyl xymeninate) active ingredient in order to improve stratum corneum hydration and blood perfusion.
Materials Innovative combinations of effective ingredients have been obtained and presented as useful for the relevant activities:
• High performance microcirculation modulator with an improvement of superficial blood vessel flow with increased blood perfusion, ideal for treatments where modification of microcirculation is present such as cellulitis, or heavy legs.
From Olax dissitiflora, a product has been purified (ximeninic acid), a long chain fatty acid with a double and triple bond (11-octandecen-9-ioic acid). By further esterification, a semisintethic fluid oil has been obtained, called ethyl ximenynate. As demonstrated by the advanced capillaroscopic technique (Laser Doppler Flussimetry), in a study on volunteers, ximeninic acid ethyl ester resulted, endowed with a vasokinetic activity due to its affinity to PUFA structure. Its usage in cosmetics is suggested for products for ameliorate circulatory disease of the legs, particularly when an alteration of capillary permeability is present, such as heavy legs, body firming and cellulite.
• High performance skin barrier recovery with better control of moisturisation and protection of epidermal barrier, restoring a deranged barrier by restructuring the intercellular lipid network and providing immediate moisturising effect on superficial stratum corneum. Ideal for any treatment where a recovery of skin barrier is necessary (such as atopic dermatitis, psoriasis, dry skin).
The possibility of having in the same cosmetic ingredient a combination of all members of the key lipid classes (i.e., cholesterol, ceramide, and free fatty acid or their precursors) can provide a useful support to managing skin barrier disorders. In particular, since barrier alterations are usually related to dry skin conditions, the association in the same compound with a humectant sugar such as trehalose can dramatically improve stratum corneum hydration. Atopic dermatitis, a condition characterised by impaired barrier function, whose main clinical feature is represented by an extremely dry skin (xerosis) can represent a useful model for investigating these properties.
Dermatological aspects
Product A INCI name: Lecithin, Ethyl Ximenynate* Ethyl ximenynate, and PUFA in general, are important factors related to trophism and the biochemical balance of the skin as they make up an integral part of cell wall lipids, building up cell membranes. As demonstrated by the advanced capillaroscopic technique (Laser Doppler Flussimetry), in a study on volunteers, ximeninic acid ethyl ester resulted, endowed with vasokinetic activity due to its affinity to PUFA structure. Ximeninic acid is able to interfere with cyclooxygenase, lipoxygenase, and phospholipase A2. This means the possibility of a change in the arachidonic acid metabolism in the sense of an increase in microcirculation, according to two different possible mechanisms of action:
• It could stimulate the conversion of arachidonic acid into eicosanoids in the dermis, and an increased level of eicosanoids is correlated with a vasokinetic action with an increase of the microcirculation.
• A second hypothesis relates to a direct action of ethyl ximenynate on the arterial smooth muscle cells.
Product B INCI name: Ceramide, Trehalose, Cholesterol, Hydrogenated Lecithin** Cholesterol is a fatty acid and is considered the main constituent of the cellular membrane, present both as an intercellular and extracellular lipid. It prevents the disorganisation of the skin bilayer. Ceramides are simple sphingolipids composed of long chain fatty acids and amino alcohols (sphingosine). They are divided into nine classes and could be contained up to 50% in the stratum corneum. They play an important role in maintaining and modulating skin barrier efficiency both as a binder of water and as sites for main polar lipids (PUFA). Their deficiency causes alteration in the skin barrier function. Trehalose (diglucose) is a naturally occurring disaccharide containing two glucose molecules bound by ?,?-1,1 linkage. It has a quality known as “cosmotropicity”, which means the ability to improve the structure of other molecules because it is able to link more water to them. In cells it protects principal structures, such as membranes, from dehydration by keeping them constantly hydrated, thus avoiding the denaturation of proteins. Trehalose or “resurrection sugar” is considered a unique molecule in nature that, through a stabilisation process, is able to revitalise plants in the desert that would otherwise be killed by drought. Hydration of the stratum corneum plays an essential role in maintaining skin suppleness and promoting barrier function integrity. Moisturisation can be delivered to the stratum corneum by several compounds such as NMFs, humectants, and lipids characterised by water-binding capacity. A new approach to the management of dry skin conditions can develop from a new ingredient which combines humectant capabilities derived from sugars, and barrier-restoring properties due to ceramides and cholesterol.
Results
Topical application of the combination product A has shown superior vasoactive capabilities by improving blood flow in superficial vessels 30 minutes after topical application, as compared to ethyl ximenynate five times more concentrated after measurements by Laser Doppler Flussimetry. This increased effectiveness can be helpful for designing topical formulations that are to be used for conditions of impaired skin microcirculation and related disorders, such as cellulite, local adiposity, heavy legs etc., where modification of microcirculation is present. In fact, modulating and improving local microcirculation at the affected sites can be of relevance to the management of this disorder as well as to other conditions characterised by impaired blood flow. Nevertheless, impairment of blood flow microcirculation is one of the primary events in the pathogenesis of cellulite (Fig. 1 and Table 1). Two studies have been carried out to assess the moisturising and barrierrestoring properties of product B. The study has been performed on 15 healthy volunteers affected by dry atopic skin. Measurements were performed by corneometry and evaporimetry to evaluate the product’s barrier-restoring properties. The study results show a significant progressive moisturising effect from the active product during the study at each visit, and versus the placebo treated area (p<0.01). Indeed, experimental data have shown that topical application of a combination product of nanoparticles (trehalose, ceramide 2, cholesterol) can increase skin capacitance up to 40% and decrease TEWL by 15% in two weeks as compared to placebo. Also, a normalised rate of barrier repair is observed. Subsequently, with the same treatment, it is possible on the one hand to restore a deranged barrier by restructuring the intercellular lipid network and, on the other hand, provide immediate moisturising effect on the superficial stratum corneum (Fig. 2 and Fig. 3). Such results point to the significant moisturising effect after use of the product. It is capable of moisturising the skin rapidly and helps to recover the skin barrier. In fact, the damaged barrier function might be restored by topical application of intercellular lipids and formulations containing lipids identical to those in the skin, and in particular some ceramide supplementation might improve deranged barrier function. Also, experimental data have shown that topical application of combination product B can increase skin capacitance up to 40% and decrease TEWL by 15% in two weeks as compared to placebo. Then a normalised rate of barrier repair is observed. Subsequently, within the same treatment it is possible on the one hand to restore a deranged barrier by restructuring the intercellular lipid network and, on the other hand, provide immediate moisturising effect to the superficial stratum corneum. The aim of the further study was to evaluate the effects on skin hydration of a moisturising product after topical application in comparison with two formulations in order to confirm its efficacy and validity when used in a cosmetic product. The evaluated effects on skin hydration in comparison with a benchmark formulation confirmed its efficacy and validity when used in a cosmetic product. In fact, the treatment with the new ingredient has shown significantly higher values as compared to the market reference (p<0.02) (Fig. 4 and Table 2).
Discussion
As for definitive results, the obtained products can be considered ideal vehicles for better delivering a reduced amount of actives, but keeping a high level of efficacy, and are examples of a new development for the incorporation of lipids into the obtained matrix.
Notes *X-Solve is a trademark of Sinerga SpA – Italy. **Tri-Solve is a trademark of Sinerga SpA – Italy. This article is based on an oral paper presented at the 25th IFSCC Congress 2008 in Barcelona.