Hyaluronic Acid

What is hyaluronic acid?

Hyaluronic acid is a major component of the extracellular matrix of most connective tissue (R). It is especially abundant in the skin, where it has a protective, structure-stabilising and shock-absorbing role (R). The body of an adult human has about 15g of hyaluronic acid, of which approximately half is located in the skin (R, R).

Hyaluronic acid is present in both the epidermis and the dermis of the skin. In fact, it is the main substance found in the dermis due to its viscoelastic properties (R, R). Yet while the dermis consists largely of extracellular matrix, the reverse is true for the epidermis, which is comprised almost entirely of keratinocytes. Hence, the actual concentration of hyaluronic acid in the matrix around the cells in the epidermis, is actually an order of magnitude higher than in the dermis (R).

Does hyaluronic acid get absorbed?

Structurally, hyaluronic acid is a glycosaminoglycan, a long, unbranched polysaccharide comprising repeated units of disaccharides, D-glucuronic acid and N-acetyl-D-glucosamine. Its molecular weight is proportional to the number of disaccharide repeats (R).

Hyaluronic acid is largely ionized at the pH prevailing on the skin, and is therefore strongly hydrophilic. This and its high molecular weight should hinder its penetration of the strateum corneum, but experiments have shown that hyaluronic acid is able to penetrate mouse, rabbit and human skin (R, R).

It turns out that hyaluronic acid in the hydrated state forms internal hydrogen bonds along its saccharide chain, creating a twisting ribbon structure with a non-polar, relatively hydrophobic face (R, R) that can increase its permeation through the stratum corneum (R). Moreover, hyaluronic acid has a considerable capacity to bind water, which is thought to enhance its absorption since increased hydration of the skin surface is known to influence its permeability (R).

Still, the molecular weight has a major influence on the skin permeation of hyaluronic acid. In one study, hyaluronic acid of low molecular weight between 20-300 kDa passed through the stratum corneum, while high molecular weight hyaluronic acid of between 1000-1400 kDa was unable to do so (R).

A carrier system making use of a skin-penetrating peptide has been shown to enhance the penetration of macromolecules like hyaluronic acid into human skin (R).