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  • Alexa Aquitato

The Importance of Hyaluronic Acid Molecular Weight in Skin Care Products

Updated: Mar 23, 2023

Hyaluronic acid (HA) is a natural polysaccharide that is widely distributed throughout the body. It is well known for its ability to bind and hold water—HA attracts water molecules and is capable of containing 10,000 times its weight in water—making it an important component in many skin care products. HA has been shown to decrease clinical signs of skin aging, reduce skin inflammation, improve skin elasticity, and support wound healing. However, an often overlooked area is the importance of the molecular weight of the HA used in skin care products and how topical hyaluronic acid is delivered.

In short, the lower the molecular weight, the deeper the HA will penetrate into the skin. But that doesn't necessarily mean that a lower molecular weight is better. Ideally, you want a range of different molecular weights so that hydrating properties are delivered to multiple layers of the skin at the same time. It's also important to consider how to deliver the various types of HA to ensure optimal efficacy.

We examine the importance of HA molecular weight and explore how the delivery system impacts the effectiveness of various products.

H2: The Different Types of Hyaluronic Acid

Hyaluronic acid has a number of benefits for the skin. It helps improve hydration by increasing the skin's ability to retain moisture, and reduces the appearance of fine lines and wrinkles by filling in spaces between collagen and elastin fibers. It also increases the production of collagen and elastin, two important proteins that play a role in keeping the skin looking youthful.

Discussion around HA often centers on three molecular weight categories: high, medium, and low molecular weight. High molecular weight HA forms a moisturizing film on the surface of the skin and provides anti-inflammatory effects. Medium molecular weight HA penetrates the skin's connective tissue. Low molecular weight HA is more stable, penetrates even deeper, and provides a lasting anti-wrinkle effect.

However, discussions often fail to mention that there are various classes of low molecular weight hyaluronic acid:

  • LMW HA (~50 kDa): Low molecular weight HA provides optimal water retention and moisturization.

  • VLMW HA (~10 kDa): Very low molecular weight HA enhances cell-to-cell contact and cohesion, reducing transepidermal water loss (TEWL).

  • ULMW HA (~3 kDa): Ultra-low molecular weight HA can penetrate the deepest layer of the skin and provide new precursors for the endogenous synthesis of the extracellular matrix.

To reap the benefits of a particular molecular weight, the HA molecules need to be delivered to the correct layer of the skin. For example, to see the full benefit of ULMW HA, these molecules need to reach the dermis layer.

H2: Optimal Delivery of Low Molecular Weight HA

One way to ensure HA reaches the desired layers of skin is to use an invasive delivery system, for example, injectable dermal fillers. However, these have downsides, including risks such as infection and filler migration. A safer, more convenient alternative is a novel topical delivery system that ensures each hyaluronic acid molecule ends up in the ideal location.

Examples of such systems include liposomes, niosomes, polymersomes, and micelles. Niosomes are ideal for HA delivery as they offer high stability and permeability and are relatively inexpensive to produce. Niosome particles are ultradeformable vesicles that can squeeze through the stratum corneum and penetrate into the deeper epidermis layers.


NIO-OLIGO HA blends hydrolyzed hyaluronic acid molecules (50 Kda) with an anti-hyaluronidase inhibitor (Kaempherol). The two are encapsulated in niosome particles which penetrate the layers of the skin (Figure 1). This new-generation anti-wrinkle complex dramatically improves the viscoelastic properties of the skin while avoiding the need for a hyaluronic acid injection system.

Figure 1: NIO-OLIGO HA particles penetrating the skin.

NIO-OLIGO HA restores the natural hyaluronic acid content, decreasing deep lines and quickly making the skin hydrated, firm, and elastic. One study used software to analyze polarized images of wrinkle deepness after application of a placebo and 2% NIO-OLIGO HA cream on half-face twice daily for 28 days. Results showed a 57% reduction in main wrinkle length at the end of the study. Under the same test parameters and analysis, the number of wrinkles was reduced by 37%. Another study used high-resolution ultrasound skin imaging (Dermascan CortEx) to examine dermal density after applying a placebo or 2% NIO-OLIGO HA daily for 28 days. NIO-OLIGO HA increased dermal density by 54%.


NIO-OLIGO 3D is a breakthrough anti-wrinkle ingredient containing three niosome vesicles, each with a different particle size and encapsulating a specific molecular weight of short HA oligomers. The different sizes of vesicles ensure that hyaluronic acid molecules optimally penetrate skin at all levels. The largest niosome particles carry LMW HA, medium particles deliver VLMW HA, and the smallest niosome particles carry ULMW HA to the deepest layers (Figure 2).

Figure 2: Three sizes of niosome particles and their penetration into the skin.

This innovative approach provides maximum anti-wrinkle efficacy with similar results to Botox. A complexion analysis of skin texture on 22 volunteers applying 2% NIO-OLIGO cream twice daily for 28 days showed a 47% improvement in skin smoothness. Another study involving software analysis of VISIA-CR polarized images after application of a placebo and 2% NIO-OLIGO 3D on half-face twice daily for 28 days showed a 41% decrease in the number of wrinkles and a 25% reduction in main wrinkle length.

H5: Conclusion

Hyaluronic acid is a powerful skin care ingredient that can provide many benefits, depending on its molecular weight. Low molecular weight HA is the most effective form for reducing wrinkles, but it must be optimally delivered to the skin to be truly effective. The NIO-OLIGO delivery system ensures that each HA molecule reaches the ideal layer of skin for maximum efficacy.

Want to discover more about how these unique ingredients can take your hyaluronic acid formulations to the next level? Get in touch today.

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