HYALURONIC ACID in a cosmetic formulation

The skin matrix is one of the most important structures in the skin. It is what would remain if you took the skin (the fibrous middle layer of the skin) and removed all cells from it. It is responsible for structural integrity, mechanical resilience, stability and many other properties of the skin. The degradation of the skin matrix and the loss of its fullness plays an important role in the development of wrinkles and other signs of skin aging. The best known components of the skin matrix are structural proteins (notably collagen and elastin), which are vital to skin health and youthfullness. However, during aging these proteins are lacking and the dermis is loosing its volume. Wrinkles become obvious and a dermal laxity results in the appearence of more marked skin grooves. In addition to the framework of structural proteins, the skin matrix also needs appropriate filling, which provide mechanical cushioning, hold moisture, enhance barrier function, and so forth. The principal skin matrix fillers are glycans, a class of glucose-based polymers that includes glycosoaminoglycans and proteoglycans. As far as skin rejuvenation is concerned, the most important glycan may be hyaluronic acid (a.k.a. hyaluronan, hyaluronate or HA).

THE STRUCTURE

Hyaluronic acid is a bio-polymer whose unit consits of D-Glucuronic acid and N-Acetyl Glucosamine. Hyaluronic acid chains can be up to 25,000 units long or even longer; their molecular weight ranging from about 5,000 to 20,000,000 Da.

Hyaluronic acid is synthesized by the enzymes called hyaluronan synthases. Humans have at least three types of hyaluronic acid synthases: HAS1, HAS2, and HAS3. HAS1 and HAS2 synthases produce high molecular weight HA whereas HAS3 produces low molecular weight HA. Hyaluronic acid is degraded by the enzymes called hyaluronidases, of which there also appear to be several types.

THE IMPORTANCE in the SKIN PHYSIOLOGY

Hyaluronic acid has many functions throughout the body, especially in the connective tissue. In the skin, some of its known roles are the following:

• Holding moisture


• Increasing viscosity and reducing permeability of extracellular fluid


• Contributing to mechanical resilience and suppleness of the skin


• Regulation of tissues repair


• Regulation of movement and proliferation of cells


• Regulation of immune and inflammatory responses

The physiological effect of hyaluronic acid largely depends on the size (molecular weight) of its chains. In particular, relatively small HA molecules (weighing less than about 20,000 Da) appear to trigger the early phases of wound healing, including activation of various types of immune cells and inflammatory responses. In tissue injury there is an increased degradation of extracellular matrix (and HA in particular). These degradation fragments (i.e. small size HA fragments) act as indicators of injury and trigger wound healing. On the other hand, large HA molecules appear to suppress local immune response and inflammation. By the similar logic, the predominance of large HA molecules sends a signal that the skin is intact and defense and/or repair are not required. This is why in the LONGIDERM formulation most of the products have medium to large chains. In special LONGIDERM formulations HA small chain are used as a carrier for other molecules such as peptides.

Hyaluronic acid and aging

The skin content of hyaluronic acid decreases with age. This contributes to the loss of moisture and the skin becomes thinner and less full. The loss of HA may also impair the skin's ability to repair itself and possibly affects the synthesis and deposition pattern of other skin matrix components.

Topical hyaluronic acid

Topical hyaluronic acid can be formulated in form of gels and serums. HA can provide effective skin surface moisturizing and can be combined with other ingredients. 

HA can penetrate into the dermis if the molecule is small enough.  Medium-to-large size HA molecules (perhaps with molecular weight above 20,000 Da) will not penetrate sufficiently to have an impact on the skin matrix. However, small size HA (5,000 - 20,000 Da) may penetrate into the dermis in significant amounts. The effect on the matrix is controversial. Assuming small size HA molecules penetrate into the dermis, they are likely to trigger some elements of the wound healing response (as we discussed above), such as immune activation, inflammation, cell division, blood vessel growth, new skin matrix synthesis and so forth. The net effect might be either matrix degradation and accelerated skin aging or matrix remodeling and improved skin texture. 

Inhibiting the degradation of hyaluronic acid

If stimulating HA synthesis is problematic or insufficient, an alternative could be to inhibit its degradation by blocking the enzyme hyaluronidase. Escin, a saponin extracted from horse chestnut is one of these actives. In a few clinical trials, it was shown to strengthen veins and improve venous insufficiency, presumably via inhibiting hyaluronidase and elastase in vein walls. It may (or may not) be able to inhibit these matrix-degrading enzymes in the skin. The other candidate, surprisingly, is a variant of a well-known skin care ingredient ascorbyl palmitate. Its isomer L-Ascorbic Acid 6-Hexadecanoate was shown to inhibit hyaluronidase in some species, including mammals.