Since its discovery, hyaluronic acid (HA) has garnered significant interest from scientists. Despite its simple chemical structure, its biological functions are extensive. Today, hyaluronic acid is widely used in cosmetics to moisturize the skin and reduce wrinkles. In aesthetic medicine, it is used as a dermal filler to add volume to facial wrinkles and hollow areas. In ophthalmic surgery, it serves as a viscoelastic agent for cataract and glaucoma surgeries, providing protection and lubrication for the eyes. In the field of orthopedics, it is used in intra-articular injections to help relieve osteoarthritis for several months. Sodium hyaluronate can be used in different fields such as skin care, medical treatment, and beauty, thanks to the different molecular weights of hyaluronic products.

Hyaluronic Acid Molecular Weight

Molecular Weight of Hyaluronic Acid

–What is the Molecular Weight of Hyaluronic Acid?

Hyaluronic acid (HA) is a naturally occurring polysaccharide molecule found in human tissues. Its molecular weight (M.W) is usually measured in Daltons (Da). The molecular weight of HA can vary greatly, ranging from a few thousand Daltons to several million Daltons. Common hyaluronic products are typically classified into high molecular weight, medium molecular weight, low molecular weight, and oligomeric hyaluronic acid based on their molecular weight.

–Methods for Measuring the Molecular Weight of HA

Gel Permeation Chromatography (GPC): GPC is one of the primary methods for measuring the molecular mass of HA. In this method, the sample is passed through a series of gel columns that separate molecules based on their size. The separated hyaluronic acid molecules are then detected in a detector to determine their molecular weight.

Light Scattering: Light scattering is another commonly used method for measuring the M.W of sodium hyaluronate. In this method, the hyaluronic acid sample solution is exposed to a laser beam, and its M.W is calculated based on the scattering pattern of the molecules.

Viscometry: This method determines the M.W of hyaluronic acid by measuring the viscosity of its solution. The molecular mass of hyaluronic acid correlates with its flow properties in solution, allowing the estimation of M.W through viscosity measurements.

Nuclear Magnetic Resonance (NMR): NMR can also be used to measure the M.W of sodium hyaluronate. By observing the NMR signals of a hyaluronic acid sample in a magnetic field, its molecular weight and molecular structure can be inferred.

Types of Hyaluronic Acid by Molecular Weight

1. High Molecular Weight HA:

• The M.W is higher than 1,800KDa
• Forms a breathable film on the skin surface, locking in moisture and preventing evaporation, providing long-lasting hydration.
• Poor penetration, does not absorb into the skin.

2. Medium Molecular Weight Sodium Hyaluronate:

• The M.W is between 200KDa and 1,800KDa.
• Forms a breathable film on the skin surface, locking in moisture and tightening the skin.

3. Low Molecular Weight Hyaluronic Acid:

• The M.W is between 5KDa and 200KDa.
• Penetrates the dermis layer of the skin, locking in moisture and promoting skin metabolism, making the skin moist, smooth, delicate, and elastic.
• Poor water retention ability on the skin surface.

4. Oligomeric Hyaluronic Acid:

• The M.W is less than 5KDa
• Composed of less than 50 monosaccharide units, with a degree of polymerization of less than 25, it can deeply penetrate the dermis layer.

Table 1 Comparison of HA with Different Molecular Weights

Table 1 compares the differences of hyaluronic acid with different molecular weights from the four dimensions of molecular weight, water solubility, moisturizing effect and durability.

Stanford Chemicals Company (SCC) is at the forefront of hyaluronic acid development, offering sodium hyaluronate powder in various molecular weights. For more information or specific applications, please visit our home page.

Common Applications of Hyaluronic Acid with Different Molecular Weights

There is currently a general view that the biological effects of hyaluronic acid depend largely on molecular mass. In the same way, hyaluronic acid is widely used in different fields depending on its molecular mass.

–Main Applications of High Molecular Weight HA

High molecular weight hyaluronic acid is mainly used in the fields of lubrication and moisturizing. It has strong moisturizing properties and biocompatibility, and is often used in medicine and cosmetics.

• Ophthalmic surgery: High molecular weight hyaluronic acid is often used as a viscoelastic agent in ophthalmic surgery (such as cataract surgery), where it can provide good lubrication and protection.
• Joint lubricant: In the treatment of osteoarthritis, as an intra-articular injection (such as SYNVISC), high molecular mass hyaluronic acid can improve the viscoelasticity of joint fluid, relieve pain and improve joint function.

–Main Applications of Medium Molecular Weight HA

Medium molecular weight hyaluronic acid is mainly used in the field of moisturizing and repairing. It has moderate moisturizing effect and good transdermal absorption, and is widely used in skin care products and medical dressings.

• Skin care products: For example, hyaluronic acid used in facial creams and essences can help the skin retain moisture, enhance skin barrier function, and promote cell regeneration.
• Medical dressings: Medium molecular mass hyaluronic acid is often used in burn and wound dressings to provide a moisturizing environment and promote wound healing.

–Main Applications of Low Molecular Weight HA

Low molecular weight HA is mainly used in the fields of permeability and anti-aging. It has better permeability and biological activity, and can penetrate deeper into the skin to stimulate cell activity.

• Anti-aging products: such as anti-wrinkle essences and eye creams. Low molecular mass hyaluronic acid can penetrate deep into the dermis, promote collagen production, and reduce fine lines and wrinkles.
• Oral supplements: Some oral hyaluronic acid supplements are designed to be absorbed through the intestines to improve skin hydration and anti-aging effects throughout the body.

–Main Applications of Oligomeric Molecular Weight HA

Oligomeric molecular weight HA is mainly used for deep moisturizing and repair. It has very high biological activity, can quickly penetrate the skin, and plays a role in cell repair and immune regulation.

• Deep moisturizing essence: In high-end skin care products, oligomeric molecular mass hyaluronic acid is often used as an active ingredient, quickly penetrating into the bottom layer of the skin to provide deep hydration.
• Regenerative repair products: such as post-traumatic repair cream or post-operative care products, oligomeric molecular mass hyaluronic acid can quickly repair the skin barrier and promote wound healing.

Conclusion

Hyaluronic acid is categorized into high molecular weight, medium molecular weight, low molecular weight, and oligomeric hyaluronic acid based on its M.W. Each type of HA, due to its unique physical and chemical properties, plays a distinct and important role in medicine and skincare products.

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This set of experiments consisted of three parts:

Firstly, four different molecular weights of hyaluronic acid (20kDa, 50kDa, 130kDa, and 320kDa) were selected and their effects were observed in terms of causing skin inflammatory reactions in pig ear skin. It was found that 20kDa significantly caused the inflammatory response in the skin. The ability of hyaluronic acid with a molecular weight of 50 kDa to cause an inflammatory response was much lower than 20 kDa and lower than 130 kDa, thus ruling out the possibility of using 20 kDa as a safe ingredient in skin care products.

The second set of experiments investigated the penetration of hyaluronic acid of different molecular weights into the skin of pig ears. It was found that the penetrating power of hyaluronic acid at 50kDa was much higher than that of hyaluronic acid at molecular weights above 300kDa.

The third group of experiments confirmed the effect of different molecular weights on skin wrinkles (anti-wrinkle effect). The results are shown below, and it is clear that 50kDa has the most pronounced anti-wrinkle effect. The article concluded that the molecular weight of hyaluronic acid can be chosen to avoid the inflammatory response of the skin caused by low molecular hyaluronic acid. Hyaluronic acid above 50 kDa has the best anti-wrinkle effect. Other large molecular weights of hyaluronic acid do not penetrate the skin well enough to be biologically effective.

In practice, it is extremely difficult to achieve a single molecular weight for hyaluronic acid used as an ingredient in skincare products, and most of these ingredients are within a range of molecular weights, which means they are all mixtures of different molecular weights. On balance, I still prefer hyaluronic acid in the 50kDa-110kDa molecular range the most. The penetration is not bad, the safety is high, and the effect is reliable. So when our company makes formulations, the low molecular hyaluronic acid ingredients are also in this range.

We can look at it this way, hyaluronic acid itself is a huge multimer, and the reason why it has a good moisturizing ability is related to its molecular weight. The higher the molecular weight the better the moisturizing ability, but the lower the penetrating ability.

The ultra-low molecular weight hyaluronic acid does not have such a good moisturizing ability. So there is no scientific basis for trying to achieve deep moisturizing with such ultra-low molecular hyaluronic acid. And the presence of such ultra-low molecular weight hyaluronic acid in the deeper layers of the skin may instead lead to inflammatory reactions in the skin through information transfer. It should be avoided as an ingredient in skin care products.

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