The different forms of hyaluronic acid used in cosmetics.

The hyaluronic acid is a highly hydrophilic complex sugar naturally present in the human body, notably in the joints, muscles, the eye and especially the skin. Indeed, nearly 50% of the hyaluronic acid in the body is located in the dermis, where it is part of the extracellular matrix and supports collagen and elastin fibres. Thanks to its ability to attract and retain water, it provides optimal hydration and contributes to the skin’s firmness.

Nevertheless, with age, the natural production of hyaluronic acid decreases by around 6% per decade, contributing to skin laxity, the appearance of wrinkles and reduced cellular activity. After 50 years, the hyaluronic acid reserve can be halved. Topical application of hyaluronic acid via cosmetic treatments therefore represent an effective strategy to compensate for this loss, in a much less invasive and risky way than an injection.

Hyaluronic acid comes in several forms, each delivering specific benefits based on its molecular size and formulation. These variations enable targeting different layers of the skin and tailoring the hydration or plumping effect as required.

• Pure hyaluronic acid (INCI: Hyaluronic Acid).

  This high molecular weight hyaluronic acid (>1,000 kDa, often >1,800 kDa) remains predominantly on the surface of the epidermis. It forms a protective film that limits water evaporation and hydrates the superficial layers. It also provides an immediate tightening effect by filling in fine lines caused by dehydration.

• Hydrolysed hyaluronic acid (INCI: Hydrolysed Hyaluronic Acid).

  This is hyaluronic acid fragmented by enzymatic or acid hydrolysis, yielding intermediate molecular weight fragments (100–1 000 kDa). These smaller molecules penetrate slightly deeper into the skin, enhance its hydration and help limit cutaneous dehydration.

• Salts of hyaluronic acid (INCI: Sodium Hyaluronate).

  Hyaluronic acid salts are stable and easy to incorporate into cosmetic formulations. Depending on their size, they may be low-molecular-weight (50–300 kDa), capable of penetrating the deeper layers of the epidermis and stimulating the skin’s natural production of hyaluronic acid. They are known to plump the skin and reduce the appearance of wrinkles, while providing long-lasting hydration. Hyaluronic acid salts can also exist in high-molecular-weight forms for a superficial protective action.

• Cross-linked hyaluronic acid (INCI: Sodium Hyaluronate Crosspolymer).

  This form is achieved by cross-linking low-molecular-weight hyaluronic acid molecules to create larger, more stable structures. It combines the efficient penetration ability of smaller hyaluronic acid molecules with the film-forming effect of larger ones, whilst offering excellent tolerability.

• Acetylated hyaluronic acid (INCI: Sodium Acetylated Hyaluronate).

  Acetylation replaces certain –OH groups with acetyl moieties, conferring both lipophilic and hydrophilic properties on hyaluronic acid. Studies have shown that it absorbs up to three times as much water as conventional hyaluronic acid, providing deep and long-lasting skin hydration. Several investigations have also demonstrated its ability to reduce the release of matrix metalloproteinase-1 (MMP-1), the skin enzymes responsible for collagen degradation, and to visibly diminish wrinkles, particularly those in the nasolabial fold and crow’s feet.

• Hydroxypropylated hyaluronic acid (INCI: Hydroxypropyltrimonium Hyaluronate).

  This hyaluronic acid modified has a particular affinity for hair, as it carries a positive charge, unlike hair fibres which are negatively charged. Consequently, it is frequently used in hair care products, especially in masks and conditioners, to provide a conditioning effect and smooth the cuticle, thereby increasing shine and helping to reduce split ends.

Hyaluronic acid is distinguished not only by its chemical structure but also by its molecular weight, another parameter that determines its behaviour on the skin.

High molecular weight forms remain predominantly on the surface: they create a protective film, limit transepidermal water loss and provide an immediate smoothing effect. In contrast, intermediate to low molecular weight hyaluronic acids penetrate more deeply into the superficial layers of the epidermis, where they enhance hydration more durably and support the maintenance of the barrier function. Very low molecular weight forms interact more closely with skin cells and can stimulate fibroblast activity, thereby promoting the synthesis of endogenous hyaluronic acid.

In practice, it is useful to combine several molecular weights of hyaluronic acid into the same treatment to act at different levels of the skin.

Several teams have investigated the cutaneous penetration of hyaluronic acid as a function of molecular weight. One study in vitro therefore aimed to comparatively evaluate the ability of twelve hyaluronic acid variants of widely differing molecular weights to traverse the skin following topical application. In this study, researchers employed a Franz diffusion-cell skin model to analyse hyaluronic acid penetration into the epidermis and dermis. The twelve forms tested ranged from very low molecular weights (400 Da to 1 kDa) to much higher ones (up to 2 000 kDa, including a cross-linked form).

The results show that all forms of hyaluronic acid are capable of traversing the skin barrier, with penetration observable as early as 30 minutes after application. However, the efficiency of this penetration varies markedly with molecular size: low-molecular-weight hyaluronic acids penetrate more effectively and deeply, particularly into the dermis, achieving cumulative rates of up to 63–78% at 24 hours, whereas high-molecular-weight forms exhibit more limited penetration, albeit still measurable.

Statistical analyses confirm a significant inverse correlation between molecular weight and skin penetration: the larger the molecule, the more limited its diffusion into the skin.

Another interesting finding is that none of the tested forms fully penetrates the skin to reach systemic circulation, suggesting a favourable safety profile of hyaluronic acid in cosmetics. This study thus supports the idea that combining different molecular weights within a single product allows action at multiple levels of the skin, providing surface hydration, structural support and deeper biological effects.

• PIOT O. & al. Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy. Ski Research & Technology (2015).

• CHEN J. & al. Preparation and applications of hyaluronic acid and its derivatives. International Journal of Biological Macromolecules (2019).

• LOGHIN F. & al. Advantages of hyaluronic acid and its combination with other bioactive ingredients in cosmeceuticals. Molecules (2021).

• SU E. & al. Current advances in the biosynthesis of hyaluronic acid with variable molecular weights. Carbohydrate Polymers (2021).

• GIARDINA S. Skin penetration ability of 12 hyaluronic acids with different molecular weights after topical application. JOJ Dermatology & Cosmetics (2023).