The different forms of hyaluronic acid in cosmetics.

The hyaluronic acid is a highly hydrophilic complex sugar naturally present in the human body, particularly in joints, muscles, the eye, and above all 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 fibers. Thanks to its ability to attract and retain water, it ensures optimal hydration and contributes to skin firmness.

Nevertheless, with age, the natural hyaluronic acid production decreases by about 6% per decade, contributing to skin laxity, wrinkle appearance, and reduced cellular activity. After age 50, hyaluronic acid reserves may be reduced by half. Topical application of hyaluronic acid via cosmetic care thus represents an effective strategy to offset this loss, in a way that is far less invasive and risky than a injection.

Hyaluronic acid is available in multiple versions, each providing specific benefits based on its molecular size and formulation. These variations enable targeting different layers of the skin and tailoring hydration or the desired plumping effect.

• Pure hyaluronic acid (INCI: Hyaluronic Acid).

  This high-molecular-weight hyaluronic acid (>1,000 kDa, often >1,800 kDa) remains primarily 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 dehydration-induced fine lines.

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

  This is hyaluronic acid that has been 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 skin dehydration.

• Hyaluronic acid salts (INCI: Sodium Hyaluronate).

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

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

  This form is obtained by cross-linking low-molecular-weight hyaluronic acid molecules, resulting in larger, more stable structures. It combines the effective penetration capacity of smaller hyaluronic acids with the film-forming properties of larger ones, all while offering excellent tolerability.

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

  Acetylation replaces certain –OH groups with acetyl groups, giving hyaluronic acid both lipophilic and hydrophilic properties. Studies have shown that it absorbs up to three times more water than standard hyaluronic acid, providing deep, long-lasting hydration to the skin. Several studies have also demonstrated that it can reduce the release of matrix metalloproteinase-1 (MMP-1), skin enzymes that degrade collagen, and visibly diminish wrinkles, especially those in the nasolabial folds and crow’s feet.

• Hydroxypropylated hyaluronic acid (INCI: Hydroxypropyltrimonium Hyaluronate).

  This hyaluronic acid modified has a particular affinity for hair, since it is positively charged, unlike hair fibers which carry a negative charge. It is therefore often used in hair care, especially in masks and conditioners, to provide a conditioning effect and smooth the cuticle, thereby enhancing shine and reducing split ends.

Hyaluronic acid is distinguished not only by its chemical form but also by its molecular weight, another parameter that conditions its behavior on the skin.

High molecular weight forms remain predominantly on the surface: they form a protective film, limit insensible 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 reinforce hydration in a more sustained manner and contribute to the maintenance of the barrier function. Very low molecular weight forms interact more closely with skin cells and can stimulate fibroblast activity, thereby promoting endogenous hyaluronic acid synthesis.

In practice, it is advisable to combine multiple molecular weights of hyaluronic acid in a single formulation in order to act at different levels of the skin.

Several teams have investigated the question of hyaluronic acid’s skin penetration relative to its molecular weight. A study in vitro thus aimed to comparatively assess the ability of twelve hyaluronic acid variants with widely differing molecular weights to permeate the skin following topical application. In this study, the researchers employed a Franz diffusion cell skin model to analyze hyaluronic acid penetration into both the epidermis and the dermis. Twelve variants were tested, ranging from very low molecular weights (400 Da to 1 kDa) to much larger forms (up to 2,000 kDa and a crosslinked form).

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

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

Another interesting finding is that none of the tested forms fully penetrate the skin to reach systemic circulation, suggesting a good safety profile of hyaluronic acid in cosmetics. This study thus supports the idea that combining different molecular weights within a single product can act on multiple skin levels, 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).