Why is Sodium Hyaluronate Used in Drug Delivery

This is mainly attributed to its distinctive physicochemical and biological properties.

Sodium hyaluronate is a linear polysaccharide containing repeating disaccharide units, which contains lots of carboxyl groups (-COOH) and hydroxyl groups (-OH). Its structure renders it highly hydrophilic. It is water-soluble and can make very viscous solutions, which suits hydrophilic drug loading. Besides, its carboxyl groups and hydroxyl groups can be chemically modified to conjugate drug molecules or functional groups to construct intelligent delivery systems. The common modification methods involve esterification, amidation, and crosslinking.

Fig 1. The structures of sodium hyaluronate and its acetylated derivatives modified by esterification[1]

The structure of sodium hyaluronate provides the basis for drug delivery, while its biological properties are the key to the choice.

Hyaluronic acid is a natural ligand for CD44 receptor, which is highly expressed on most tumor cells, inflammatory tissues, and stem cells. HA-modified drug delivery systems are able to actively target these diseased tissues, enhancing local drug concentrations. CD44 is like a signal beacon, guiding HA to the locations of disease. Once the HA-coated drug reaches the target, it must be released in order to function. This is where the next key player enters: hyaluronidase. This enzyme degrades HA and, conveniently, is highly active in tumor or inflamed tissue. In the presence of hyaluronidase, the HA carrier degrades, releasing the therapeutic payload.

Hyaluronic Acid or Sodium Hyaluronate?

In the application of drug delivery systems, sodium hyaluronate is utilized instead of hyaluronic acid. Because the sodium salt form is more stable and more soluble in water at neutral or alkaline pH.

What Value Does Sodium Hyaluronate Coating Offer for Drug Delivery

1. Targeted Delivery

Shell drug carriers with HA enable selective binding to such receptors, enabling targeted delivery of the drugs to the disease cells or tissues. For example, HA-coated nanoparticles can deliver chemotherapy drugs specifically to tumor cells with less damage to healthy tissues and fewer side effects.

2. Enhanced Stability and Controlled Release

Sodium hyaluronate coatings protect encapsulated drugs from premature degradation and stabilize delivery systems. The viscoelastic formation of solutions by HA and the mucoadhesive properties enable sustained, controlled drug delivery with extended preservation of therapeutic levels at target sites. For instance, HA has been used to prepare sustained-release protein and peptide formulations, where traditional carriers like PLGA can cause inflammation and protein denaturation.

3. Versatility and Adaptability

Sodium hyaluronate coatings are biocompatible with multiple drug carriers, ranging from nanoparticles and liposomes to micelles. It is chemically tunable and may be conjugated with various therapeutic molecules such as small-molecule drugs, proteins, and nucleic acids. HA coatings may also be made responsive towards specific stimulants (e.g., pH or temperature stimuli), enabling controlled drug release at targeted locations.

4. Reduced Immunogenicity

As a naturally occurring substance in the human body, HA is biocompatible. It is less likely to trigger immune responses than synthetic materials. Sodium hyaluronate-coated nanoparticles are least familiar and recognized by the immune system, enhancing their shelf life and stability in the blood circulation for better target delivery.

Applications of Sodium Hyaluronate Coating in Drug Delivery

• Cancer treatment: Targeted drug delivery of chemotherapy drugs to cancer cells while minimizing systemic toxicity.
• Ocular drug delivery: Increasing the residence time and bioavailability of drugs in the eye for conditions such as glaucoma and dry eyes.
• Wound healing: Encouraging tissue repair and regeneration by delivering growth factors and other biomacromolecules to the injured area.
• Inflammatory arthritis treatment: Inflamed joint delivery of anti-inflammatory agents to alleviate inflammation and pain.
• Gene therapy: Enhancing the delivery efficiency and stability of gene vectors for targeted gene expression or silencing.
• Transdermal drug delivery: Enabling drug penetration through the skin for local and systemic delivery.

Conclusion

Sodium hyaluronate coatings are a powerful instrument in modern drug delivery that combines natural targeting functions with designed specificity. Employing HA’s inherent physicochemical properties and biological interactions, researchers can design systems to maximize therapeutic benefit while minimizing side effects. For more information, please check Stanford Chemicals Company (SCC).

[1] Chen, Fan & Guo, Xueping & Wu, Yue. (2023). Skin antiaging effects of a multiple mechanisms hyaluronan complex. Skin Research and Technology. 29. 10.1111/srt.13350.

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1. What Is Salicylic Acid?

Salicylic acid is a beta-hydroxy acid (BHA) derived from willow bark. It is oil-soluble, meaning it can penetrate deep into pores to dissolve excess sebum and dead skin cells.

Key Benefits of Salicylic Acid:

• Exfoliates the skin: Helps unclog pores and remove dead skin cells.
• Destroys acne: Deflates blackheads, whiteheads, and pimples by dissolving excess oil.
• Anti-inflammatory: Cools redness and inflammation of the acne.
• Enhances skin texture: Smooths out roughness and reduces the appearance of large pores.

Best For:

• Acne and oily skin
• Whiteheads and blackheads sufferers
• People with mild to moderate acne

Possible Side Effects:

• Can lead to dryness or irritation, particularly on sensitive skin
• Can make skin more sensitive to the sun, always use sunscreen.

The structure, origin, nature, and use of salicylic acid have been discussed in great detail in the preceding article, so we will not discuss them here. Interested readers can visit:

Salicin vs Salicylic Acid: Relationship, Difference & Uses

2. What Is Hyaluronic Acid?

Hyaluronic acid (HA) is a humectant, a water-absorbing molecule. It occurs naturally in the skin and provides hydration by holding up to 1,000 times its weight in water.

Major Advantages of Hyaluronic Acid:

• Deep hydration: Moisturizes and fills the skin, leaving it less dry.
• Improves skin elasticity: Makes the skin look youthful and soft.
• Soothes irritation: Gently calms sensitive or dry skin.
• All skin types may use light hydration, even oily skin.

Best For:

• dry, dehydrated skin
• Aging skin (keeps the skin from forming fine lines and wrinkles)
• sensitive or inflamed skin
• All skin types, even oily, as it is non-comedogenic.

Possible Side Effects:

• Seldom irritates, one of the gentlest skincare ingredients.
• Will take moisture out of the skin in extremely dry conditions if not sealed with a moisturizer.

For details on the properties, applications, benefits, and characteristics of hyaluronic acid, please refer to these articles:

Top 10 Benefits of Hyaluronic Acid

What is Hyaluronic Acid Powder? Benefits and Usage

Why Is Hyaluronic Acid Important?

High VS. Low Molecular Weight Hyaluronic Acid

3. Salicylic Acid vs. Hyaluronic Acid

Key Differences

Can You Use Them Together

The answer is yes. These two ingredients actually work very well in combination. Salicylic acid helps clean out your pores and stops breakouts from forming. In the meantime, hyaluronic acid restores moisture that might be stripped away while exfoliating. This creates a well-rounded skincare routine that treats acne without dehydrating the skin.

Which One Should You Choose

The best ingredient for you will be based on your skin type and concerns. For oily, spot-prone skin or pores that easily clog, salicylic acid is best. For skin that’s likely to be dry or dehydrated, hyaluronic acid is better suited. For most people, they find they need both – salicylic acid for spots and hyaluronic acid for staving off dryness. The combination approach enables you to reap the benefits of acne treatment while still having healthy, hydrated skin.

Final Verdict

Salicylic acid and hyaluronic acid serve totally different purposes but can beautifully complement one another. Salicylic acid is your go-to for breakout clearing, and hyaluronic acid helps to keep your skin hydrated and plump.

If you’re dealing with acne, incorporate salicylic acid carefully, and always follow up with hyaluronic acid to prevent dryness. For those with dry or aging skin, hyaluronic acid alone can provide a major hydration boost.

About Stanford Chemicals Company (SCC)

Stanford Chemicals Company (SCC) supports businesses and research communities with such critical compounds as sodium hyaluronate, salicin, salicylic acid, dihydromyricetin, and chondroitin sulfate.

If you need quality substances, we’d be delighted to help. Feel free to contact us for more details.

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Medical-Grade vs. Injectable-Grade Sodium Hyaluronate: Different Applications

Hyaluronic acid is typically classified into four grades based on its usage: food-grade, cosmetic-grade, medical-grade, and injectable-grade. Some brands are lumping medical-grade and injectable-grade into a single category. SCC particularly classifies medical-grade HA for non-injectable medical applications, such as surgical anti-adhesives barrier, wound dressings, and ophthalmic solutions.

Medical-grade sodium hyaluronate is widely used in non-injectable medical fields:

• As a moisturizing agent in eye drops used in ophthalmic preparations to treat dry eye syndrome.
• As a wound-healing accelerator in topical creams and ointments, and also in ulcer and burn dressing applications.
• As a protective layer in medical-grade hyaluronic acid in nasal sprays to relieve dryness and inflammation.
• As a smart carrier for targeted and sustained drug release in drug delivery systems with hyaluronic acid of various molecular weights.

In addition, medicinal-grade HA is most commonly used in oral care products, gynecological products, and surgical anti-adhesion membranes.

Medical-grade sodium hyaluronate applications

Injectable-grade sodium hyaluronate, on the other hand, is specifically designed for direct injection into the human body:

• It is the main component of dermal fillers utilized in treatments like rhinoplasty, lip augmentation, and facial redefinition in medical aesthetics. Its rheological characteristics and stability in vivo are carefully controlled such that it is effective and degradable in a safe way.
• Injectable-grade hyaluronic acid is injected intra-articularly in orthopedics to treat osteoarthritis, providing joint lubrication, pain relief, and repair of cartilage.
• As an ophthalmic surgery viscoelastic device, injectable-grade hyaluronic acid of high purity maintains intraocular space and protects corneal endothelial cells in anterior chamber and vitreous surgery.
• It is used in anti-adhesive agents and promoters of wound healing that have to be in direct contact with sterile human tissue.

Injectable-grade sodium hyaluronate applications

Read more: 4 Grades of Hyaluronic Acid Raw Material Comparison

Injectable-Grade Sodium Hyaluronate Needs Stricter Requirements

Injectable-grade sodium hyaluronate is administered directly into the body and represents the highest level of quality control in the industry. These products must adhere to rigorous pharmacopoeial specifications, with each batch of production undergoing full physicochemical and biological testing.

• Molecular weight control: Injectable-grade sodium hyaluronate is typically restricted to a narrow range of 1,000–2,400 kDa to ensure consistent in vivo degradation rates and clinical performance.
• Endotoxin limits: Must be below 0.05 EU/mg—ten times more stringent than medical-grade standards (typically ≤0.5 EU/mg).
• Sterility assurance level (SAL): Requires 10^-6, i.e., not more than a single viable microorganism per million units, to provide absolute safety for direct human injection.

By comparison, medical-grade sodium hyaluronate follows relatively lenient pharmaceutical excipient standards:

• Adjustable molecular weight: Can be customized from low (50–100 kDa) to ultra-high (>2,500 kDa) based on application needs.
• Endotoxin level: Generally ≤0.5 EU/mg, which is sufficient for non-injectable use.
• Sterilization: Terminal sterilization is not a necessity; quality control places greater emphasis on chemical purity, protein residuals, and heavy metal content.

This differentiated standard makes medical-grade hyaluronic acid more cost-effective for large-scale pharmaceutical production.

Hyaluronic acid injection into the joint

Conclusion & Selection Guidelines

Medical-grade and injectable-grade sodium hyaluronate represent two fundamentally distinct product standards and application philosophies. For healthcare professionals and product developers, the appropriate selection should be based on the following key considerations:

1. The application method determines grade selection.

Any application requiring direct injection into the human body must use injectable-grade HA, including dermis, joint cavities, intraocular use, etc. For applications not involving direct contact with sterile tissues, medical-grade products may be considered.

2. Risk-benefit balance.

While injectable-grade sodium hyaluronate carries higher costs, it provides essential safety assurance for high-risk applications. Of course, medical-grade products can offer more cost-effective solutions in appropriate application scenarios.

3. Regulatory compliance.

Product registration categories and regional regulatory requirements directly influence HA grade selection. Target market regulations must be thoroughly understood in advance.

4. Product performance requirements.

HA with different molecular weights exhibits distinct rheological properties and bioactivity. The optimal product specifications should be selected based on intended functional requirements.

Stanford Chemicals Company (SCC) provides medical-grade and injectable-grade sodium hyaluronate products for comprehensive solutions tailored to diverse professional needs.

Please refer to the sodium hyaluronate product COA certificates from SCC:

• Injectable-grade sodium hyaluronate powder COA
• medical-grade sodium hyaluronate powder COA

Send us an inquiry now.

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What Sodium Hyaluronate Is

First, let’s find out what sodium hyaluronate is.

Sodium hyaluronate is the sodium salt of hyaluronic acid (HA), a naturally occurring polysaccharide macromolecule found universally throughout our bodies, particularly in the skin, joints, and eyes. Focusing on the HA molecular structure, it resembles a long, knotted rope. The “knots” can relax in water to form a three-dimensional “molecular sponge network.” It’s this extremely unique structure that renders HA’s water-binding capacity simply phenomenal. Scientific research indicates that a mere 1 gram of hyaluronic acid can retain between 500 to 1000 grams of water! No surprise it’s at the top in the world of hydration!

Aside from skincare, this multi-purpose ingredient also plays a crucial part in medical aesthetics, nutraceuticals, and even luxury textiles. But today, let us talk about its top-billed job in skincare.

What Are the Benefits of Sodium Hyaluronate for the Skin

High-molecular-weight sodium hyaluronate forms a breathable film over the skin surface, holding moisture in without excluding external bacteria, dust, and UV light. On the other hand, low-molecular-weight sodium hyaluronate penetrates deeply into the dermal layer, promoting nutrient absorption, enhancing the elasticity of the skin, and reducing aging.

1. Hydration

Sodium hyaluronate is extremely hydrophilic and forms a water-retaining barrier on the skin that is extremely efficient in retaining water. Its action is also adjustable based on environmental conditions: it holds most water at low relative humidity (33%) and least at high humidity (75%). As a result of this property, it enables optimal performance under diverse climatic conditions.

2. Skin Repair

When skin is harmed by sunburn, UV damage, redness, darkening, or peeling, sodium hyaluronate is to the rescue with firm support. It promotes epidermal cell proliferation and differentiation, promotes cell regeneration, and scavenges free radicals. This accelerates the healing of injured tissues at a faster rate, promoting skin regeneration and wound healing.

3. Anti-Wrinkle

About 50% of the sodium hyaluronate in the body resides in the dermis. Mixed with collagen and elastin, it forms a powerful matrix that gives skin stability and elasticity. However, HA content lessens, collagen decreases, and the skin’s ability to retain moisture diminishes with age, leading to wrinkles.

Sodium hyaluronate solutions possess high viscoelasticity and lubricity, creating a hydrating, permeable film that keeps the skin hydrated and radiates. Penetration of low-molecular-weight HA into the dermis increases microcirculation and augments the uptake of nutrients, all of which work towards anti-aging and wrinkle reduction.

Reading more: Hyaluronic Acid and Collagen: The Perfect Combination for Healthy Skin

4. Nutrition

Sodium hyaluronate is a natural compound present in the skin. Externally applied, it restocks the body’s endogenous HA store. The lesser molecular weight of HA allows easy absorption in the blood and dermis, replenishing the level of hyaluronic acid, lowering dryness, and maintaining nutrient delivery and waste removal, hindering skin aging and promoting beauty effectively.

To understand the difference between endogenous HA and exogenous HA, please read this article: Does Hyaluronic Acid Cause Cancer

Long-term popularity of sodium hyaluronate is not hype but solid scientific efficacy.

Stanford Chemicals Company (SCC) is a professional hyaluronic acid supplier, providing high-quality products and services to global clients in pharmaceuticals, skincare, and food industries. SCC specializes in the development, production, and distribution of cosmetic-grade HA, food-grade HA, medical-grade HA, chondroitin sulfate, dihydromyricetin, and more.

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You know that tangy, refreshing taste of lemons and oranges? That’s partly thanks to citric acid—a natural compound found in citrus fruits. When this zesty acid teams up with minerals like calcium, magnesium, or sodium, they form what scientists call “citrates.”

These versatile compounds are like the Swiss Army knives of the chemical world. Because they dissolve easily, stay stable, and play nice with our bodies, you’ll find them working behind the scenes in everything from sodas to medications.

Citrates generally exhibit the following properties:

• High water solubility: Easily dissolves in water, making it suitable for liquid medications or food additives.
• Chelation: Binds metal ions to prevent oxidation or precipitation, serving functions like anticoagulation and water softening.
• pH regulation: Some citrates are weakly alkaline and can adjust the acidity or alkalinity of food or pharmaceuticals.

Why Are Citrates Important?

Citrates play a crucial role in food, pharmacy, chemical technology, and biological metabolism.

1. They are widely used in food processing as preservatives, acidity regulators, and stabilizers.
2. They have critical roles in the medical area, which include:

• Sodium citrate in blood transfusions to prevent clotting,
• Calcium citrate for calcium supplementation,
• Ferric Citrate for iron supplementation,
• Potassium citrate for the prevention of kidney stones,[1]
• Magnesium citrate for treating constipation.

3. They are also significant players in biological metabolism. Citrate is a critical intermediate of the tricarboxylic acid (TCA) cycle in human organisms, with a direct role in energy metabolism.[2]
4. Owing to their metal-chelating property, citrates find applications in heavy metal removal in industrial wastewater treatment.

4 Common Types of Citrates

Different citrates have different applications and activities depending upon which metal ions they chelate.

1. Sodium Citrate

Sodium citrate is the most important citrate, which is produced primarily by fermentation of starchy material to yield citric acid and then neutralizing it with alkaline substances. Since its raw material is grain, it is totally safe and innocuous to human health.

Sodium citrate finds application in a wide range:

• Anticoagulant: Used in blood transfusion or storage by chelating calcium ions with a view to preventing clotting.
• Retarder: Similarly, in construction, sodium citrate can be added to concrete as a retarder, improving freeze resistance, compressive strength, and tensile performance.
• Food additive: Controls acidity (e.g., in carbonated drinks, jams) or acts as an emulsifier (e.g., in cheese).
• Urinary alkalinizer: Prevents uric acid stones and enhances the solubility of certain drugs (e.g., antibiotics).
• Electroplating: Environmentally friendly, low-maintenance, minimally corrosive, high-quality coatings are the outcomes of neutral citrate nickel plating.

2. Magnesium Citrate

Magnesium citrate is a compound of magnesium carbonate and citric acid. Doctors often prescribe it as a supplement for magnesium deficiency. Magnesium citrate has better absorption and bioavailability compared to magnesium oxide or sulfate. Medically, it draws water into the intestines to cause motility and thus is a good laxative to relieve constipation.

Functions:

• Laxative: High doses promote bowel movements for constipation or colon cleansing.
• Magnesium supplement: Prevents magnesium deficiency. Magnesium is the fourth most abundant mineral in the body, half of which is deposited in bones and teeth, and the rest in tissues and vital organs. It aids in the production of energy, supports brain and heart function, and helps maintain stable blood pressure.
• Food stabilizer: Included in beverages and nutritional supplements.

3. Calcium Citrate

Calcium citrate is an organic food supplement compound. It is better absorbed than inorganic calcium and is used as an ingredient in numerous foods like infant formula, juices, dairy, powdered drinks, sports beverages, milk, soy milk, supplements, and cereal. Its absorption is stomach acid-independent, so it is suitable for people with low stomach acid, particularly when taken on an empty stomach.

4. Ferric Citrate

Ferric Citrate（Iron citrate）is an iron ion-citric acid compound FeC₆H₅O₇. It is a water-soluble iron salt widely used in medicine, food fortification, and industry.

Applications:

• Iron supplement: For the treatment of iron-deficiency anemia. Kindler is on the stomach than ferrous sulfate.
• Food fortifier: Applied to cereals and powdered milk to fortify with iron.
• Water treatment: Applied to remove heavy metals or phosphates from water.

Comparison with Other Iron Supplements:

Stanford Chemical Company (SCC) is a trusted supplier specializing in hyaluronic acid, herbal extracts, and food additives. We provide high-quality citrates tailored to your needs. For more product details, please visit: Citrates

People Also Ask

Q1: What’s the difference between citrate and citric acid?

A: Citric acid is a free acid with a sour taste, while citrates are its metal ion-neutralized forms, typically less bitter in flavor and more practical.

Q2: Does magnesium citrate really relieve constipation?

A: Yes. High-dose magnesium citrate increases intestinal water content, allowing for bowel movements. It’s typically taken for temporary constipation relief or colon cleansing.

Q3: Which is better for calcium supplementation—calcium citrate or calcium carbonate?

A: Low stomach acid patients should take calcium citrate. Calcium carbonate is of greater calcium value but has to be taken with food for optimal absorption.

Q4: Why does sodium citrate prevent blood clotting?

A: It sequesters calcium ions, which are essential for clotting, in the blood and does not allow coagulation. That’s why it’s used with blood storage for transfusions.

Q5: Are there natural sources of citrate?

A: There are trace amounts of natural citrates found in citrus fruits, but industrially used citrates are chemically synthesized.

Read more:

Case Study: SCC Supplies Ferric Ammonium Citrate with 20.5-22.5% Iron Content

[1] Ettinger B, Pak CY, Citron JT, Thomas C, Adams-Huet B, Vangessel A. Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol. 1997 Dec;158(6):2069-73. doi: 10.1016/s0022-5347(01)68155-2. PMID: 9366314.

[2] Choi I, Son H, Baek JH. Tricarboxylic Acid (TCA) Cycle Intermediates: Regulators of Immune Responses. Life (Basel). 2021 Jan 19;11(1):69. doi: 10.3390/life11010069. PMID: 33477822; PMCID: PMC7832849.

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What is Food Additive?

Different countries have varying definitions of food additives. The U.S. Federal Food, Drug, and Cosmetic Act (FD&C Act) defines food additives as:

Any substance directly or indirectly added to food that may become part of the food or affect its characteristics (including substances used in production, processing, packaging, transport, or storage), unless the substance is exempt (e.g., GRAS substances or prior-sanctioned substances).

Food additives have the following three characteristics:

• They are added to food and are not usually consumed alone as food.
• They include both synthetic and natural substances.
• They are added to improve food quality, color, flavor, and aroma, or for preservation and processing purposes.

What are The Types of Food Additives?

Different countries classify food additives differently. Below is a classification based on function.

1. Antioxidants

Antioxidants are additives used to delay or prevent food oxidation. They are classified as direct food additives. Their mechanisms vary:

• Some (like vitamin E) are easily oxidized, reacting with oxygen first to protect food.
• Others release hydrogen ions to break down peroxides formed during fat oxidation.
• Some bind to peroxides, interrupting the oxidation process.

2. Preservatives

Preservatives inhibit microbial growth and extend shelf life. They are divided into chemical and natural preservatives.

2.1 Chemical Preservatives are synthetic, strong antimicrobial effects, low cost, but some have usage limits.

2.2 Natural Preservatives are extracted from plants, animals, or microbes. They are safer but costlier.

3. Color Additives

Color additives enhance or restore food color. They are classified as natural or synthetic.

3.1 Natural Colors are safer but less stable, prone to fading.

3.2 Synthetic Colors are vibrant, stable, low-cost, but some may be harmful.

The U.S. primarily uses synthetic colors labeled with FD&C codes (e.g., Red 40, Yellow 5). While controversial, the FDA deems them safe in regulated amounts. Consumers can check labels and opt for natural alternatives.

4. Thickeners

Thickeners improve texture and viscosity, for example, pectin or gelatin in yogurt to prevent whey separation. Natural thickeners are now the industry standard.

5. Flavor Enhancers

Flavor enhancers amplify or improve taste. MSG is the most widely used in the U.S.

Which Are Safe?

The following table summarizes the safety information of the common food additives mentioned in the article.

If you have any requirements for the above-mentioned food additives, please feel free to contact us via email at [email protected] or submit an Inquiry. Stanford Chemicals Company (SCC) will make every effort to provide products that meet your needs.

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Hyaluronic acid (hyaluronan, HA) is a naturally occurring polymer that is constantly being synthesized and degraded in the human body. It is found predominantly in the extracellular matrix, vitreous humor, and cartilage. A typical 70 kg adult contains about 15 grams of HA, with about 5 grams metabolized and replaced daily. Surprisingly, nearly half of the whole body’s HA can be found within the skin, where its relatively brief half-life is 24 to 48 hours.

Owing to its excellent ability to retain moisture, lubricate, and support tissue repair, hyaluronan has been extensively used in dermatology, joint care, and drug delivery systems. Yet, how exactly is HA broken down and absorbed after ingestion or injection?

Absorption Pathways of Hyaluronic Acid

Hyaluronic acid (HA) is a linear polymer that is composed of repeating disaccharide units, and its absorption is also correlated with molecular weight. Research has indicated that low-molecular-weight HA (<50 kDa) would be absorbed by intestinal epithelial cell endocytosis or colonic microbiota degradation. High-molecular-weight HA is degraded by intestinal hyaluronidase to create smaller peptides, which are absorbed into the bloodstream.

Oral hyaluronic acid (HA) is primarily broken down in the intestine by enzymes and gut microflora into short molecular fragments, which are absorbed into the bloodstream. These fragments are able to activate skin and joint cells to increase endogenous HA synthesis, resulting in hydration and joint health benefits.

Fig 1.  The process of food-grade HA being absorbed by the human body [1]

Subcutaneous or intra-articular injection is the most common clinical and medical aesthetic application of HA. As injected HA is deposited inside tissue or fluid in the body, destruction and removal are primarily dependent on local enzymic hydrolysis and lymphatic drainage.

Degradation Mechanisms of Hyaluronic Acid

Molecularly, hyaluronic acid consists of two monosaccharides: N-acetylglucosamine and sodium glucuronate (Figure 2). The disaccharide components are connected linearly by β-1,4-glycosidic bonds. Bond cleavage underlies the depolymerization of HA, depending on enzyme activity and free radical degradation.

Fig 2. Structure of Hyaluronic Acid

(1) Role of Hyaluronidase

Hyaluronidases (such as HYAL1 and HYAL2) are the primary enzymes responsible for the breakdown of HA. They hydrolyze glycosidic bonds preferentially, breaking down HA to smaller oligosaccharides. They are extensively distributed in tissues like skin, liver, and spleen, so that injected HA will be gradually metabolized and eventually eliminated in urine or further broken down.

Fig 3. Degradation Pathways of Hyaluronic Acid

(2) Free Radical Degradation

Besides enzymatic degradation, hyaluronic acid is also degraded by oxidative stress resulting from reactive oxygen species (ROS) and other free radicals. Oxidative stress increases in inflamed or aged tissues, where glycosidic bond cleavage through ROS occurs frequently.

(3) Factors Influencing HA Degradation Rate

The rate at which HA breaks down in the body depends on several key factors:

• Molecular weight: High-molecular-weight HA degrades more slowly than its low-MW counterpart.
• Crosslinking: Chemically crosslinked HA (e.g., in dermal fillers) resists enzymatic breakdown, extending its longevity.
• Injection site: Areas with high blood flow (e.g., lips) metabolize HA faster than low-circulation regions (e.g., joints).
• Individual variability: Age, metabolic rate, and natural hyaluronidase levels all influence degradation speed.

Why Does the Skin Need Hyaluronan Supplementation?

Hyaluronan turnover in the skin is a quiet balance between synthesis and degradation. HA is synthesized by mesenchymal cells via the activity of hyaluronic acid synthases (HAS-1, HAS-2, HAS-3) and is degraded simultaneously by hyaluronidases. With time, this equilibrium is disturbed—degradation is greater than synthesis, leading to a decrease of HA.

To offset this deficit, topical HA skin-care products and injectable dermal fillers are used to restore missing HA and rehydrate and structurally maintain aging skin.

Stanford Chemicals Company (SCC) is a supplier with over 10 years of expertise in hyaluronic acid. If you’d like to learn more about hyaluronic acid or are interested in purchasing sodium hyaluronate powder, please feel free to contact us.

FAQs

1. How does the body absorb hyaluronic acid?

Only the low molecular weight HA molecules (below 50 kDa) are absorbed when taken orally, whereas larger molecules are broken down first. Injected HA stays put until it is slowly broken down by enzymes.

2. What breaks down hyaluronic acid in the body?

Special enzymes called hyaluronidases break down HA naturally. The enzymes cut the HA molecules into pieces that the body can either reuse or eliminate. Active oxygen molecules are also capable of breaking down HA faster, especially in older or inflamed tissue.

3. Why does injected HA persist longer than topical HA?

Injected HA forms a depot under the skin that lasts a long time to weeks to months to be metabolized. Topical HA is only able to penetrate as far as the surface layers and is removed or degraded much faster since it doesn’t deeply penetrate.

4. Why does HA degrade more rapidly?

HA is degraded faster in highly mobile tissues (like lips), in younger people who possess more active enzymes, and in inflamed tissue in where oxygen radicals and enzymes increase. Crosslinked HA, which is used in fillers, breaks down more slowly than native HA.

5. Do you slow the degradation of HA?

Yes. Avoiding excessive sun exposure, avoiding smoking, and using antioxidants (like vitamin C) can safeguard HA.

6. Why do we need to replace HA as we age?

Our own bodies make less HA and degrade it more rapidly after about age 25. This causes drying skin and crunchier joints. HA added to treatments or skincare replenishes this natural loss.

7. Is broken-down HA poisonous?

No. The body either recycles the small pieces of HA or simply expels them harmlessly.

Yes. Exercise in moderation increases HA production in joints, but extremely intense exercise can increase inflammation and HA breakdown in the short term.

[1] Xueli Zheng, Botao Wang, Xin Tang, Bingyong Mao, Qiuxiang Zhang, Tianmeng Zhang, Jianxin Zhao, Shumao Cui, Wei Chen, Absorption, metabolism, and functions of hyaluronic acid and its therapeutic prospects in combination with microorganisms: A review, Carbohydrate Polymers, Volume 299, 2023, 120153, ISSN 0144-8617, https://doi.org/10.1016/j.carbpol.2022.120153.

The post How Hyaluronic Acid is Absorbed and Degraded in the Human Body appeared first on Stanford Chemicals.

Notably, this product has been certified by the FDA, ISO9001, ISO22000, KOSHER, and HALAL, which proves that it adheres to the highest global standards for pet foods. This is a testament to SCC’s zeal to strive for scientific innovation, but at the same time, not forget practicality.

Case Study: Ferric Ammonium Citrate with 20.5-22.5% Iron to Meet Customer Needs

The Challenge: Higher Iron Content Than Market Standards

Food additive commercial brown ferric ammonium citrate usually has an iron content of 16.5% to 22.5%. It is a mild iron fortifier and is superior in safety and palatability. A manufacturer of pet feeds approached us for raw material of higher iron concentration (20.5-22.5%). The higher iron concentration will allow more iron to be supplied at the same dosage rate, thus being more appropriate for premium product production.

SCC’s Solution: Ferric Ammonium Citrate with 20.5-22.5% Iron

To meet the desired iron content, we improved the process of crystallization to eliminate moisture and impurities. Each batch of production was tested for iron content certification, as well as final quality check before dispatch. The product was thoroughly checked to ensure compliance with FDA regulations, ISO 9001/22000 quality systems, and KOSHER/HALAL certification.

Results: Meeting Customer Expectations

The optimized ferric ammonium citrate consistently hit the target iron content range and showed better stability. This third-party certified product is a source of a high-iron ingredient for pet food processors with rigorous standards of quality ensured by total documentation, such as Certificates of Analysis (CoA) and quality management certifications.

* If you’re seeking high-purity food additive ingredients, consult SCC for customized solutions.

What is Ferric Ammonium Citrate?

Ferric ammonium citrate is a compound formed by the reaction of citric acid, iron ions, and ammonia, belonging to the category of organic iron. It is basically an iron supplement of chemical synthesis origin that has widespread usage in the food industry as well as the pharmaceutical industry.

Ferric ammonium citrate is typically classified into two grades based on iron content and application: brown ferric ammonium citrate and green ferric ammonium citrate. Their iron content requirements are as follows:

1. Brown Ferric Ammonium Citrate: Also known as Ammonium Iron (III) Citrate, usually 16.5%~18.5% iron content, with the chemical formula C₉H₁₁FeN₂O₈·2H₂O. Specifications for food-grade reddish-brown ferric ammonium citrate require an iron content between 16.5% and 22.5%.

• Characteristics:Contains trivalent iron (Fe³⁺), appears reddish-brown or brownish-red, and is highly soluble in water.
• Applications:Primarily used in medical iron supplements and food additives.

2. Green Ferric Ammonium Citrate: Usually 14.5%~16.0% iron content.

• Characteristics:Contains some divalent iron (Fe²⁺), appears green or bluish-green, and is highly photosensitive.
• Applications:Mainly used in photosensitive materials (e.g., blueprint paper) and laboratory reagents.

What Are the Benefits of Ferric Ammonium Citrate?

The primary benefit of ferric ammonium citrate is its iron-supplementing function. Iron is an essential trace element, and it plays a crucial role in hemoglobin production, oxygen transportation, and the metabolism of cells. When you frequently experience fatigue, dizziness, or pale complexion, this may be a sign of iron-deficiency anemia. When this happens, ferric ammonium citrate proves to be very effective. Given this functional advantage, ferric ammonium citrate has also been used as a fortification agent in cereals, infant formula, and various nutritional products to enhance their iron content.

Beyond iron supplementation, it offers other benefits:

• Antioxidant Properties:It can delay fat oxidation in certain foods, extending shelf life.
• Color Enhancement:In some cured foods, it helps maintain a red appearance, making the product more visually appealing.

How Does Ferric Ammonium Citrate Compare to Other Iron Salts?

In addition to ferric ammonium citrate, other common iron supplements include ferrous sulfate, ferrous gluconate, and amino acid-chelated iron. How does ferric ammonium citrate compare? Below is a comparison of these four iron salts in terms of bioavailability, gastrointestinal irritation, stability, and price:

From the table, we can see the advantages of ferric ammonium citrate:

1. High Absorption Rate: As a highly soluble iron salt, ferric ammonium citrate is marked by extremely high bioavailability within the human body. With rates of absorption reaching up to 90%, it is transformed more efficiently into biologically active iron for physiological use.
2. Gentle on Digestion: Compared with ferrous sulfate, ferric ammonium citrate causes minimal gastrointestinal irritation, being more tolerant in the gut. This makes it particularly suited for individuals prone to GI upset from iron supplements.
3. Oxidation Resistance: The product exhibits superior oxidative stability under room conditions. Not only does this promote shelf life, but it also retains potency even when air is exposed during use, inhibiting active ingredients from breaking down.

Is Ferric Ammonium Citrate Safe?

As a synthetic compound used in food applications, safety is crucial. Ferric ammonium citrate has received safety approval from major food regulatory authorities including the FDA and EFSA. This certification ensures its safe use both as a dietary supplement and nutritional additive. However, excessive iron intake causes side effects ranging from upset stomach, diarrhea, or even iron poisoning. It should therefore be consumed within the appropriate recommended dosages.

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Defense Federal Acquisition Regulation Supplement is a regulatory system that gives guideline to the procurement of defense sector government. It is an extension of overall federal regulation on procurement. The supplement has strict product and services specifications. It encompasses a large umbrella of suppliers. These are companies that offer equipment, technology, and other services to the government. The guidelines encourage equal contracts and proper spending of the tax dollar.

This set of rules guarantees safety and reliability. It creates binding supplier requirements. Its simplicity can be used by small stores and even large companies. Defense Federal Acquisition Regulation Supplement is a shield that maintains the integrity and equity of government contracting.

Why is DFARS Important?

The importance of the DFARS is that it is an excellent guide to the procurement of defense. It makes all the contracts open and equitable. The regulations protect public funds by imposing strict policies at the time of acquisition. The regulations are an insurance against errors and oversights.

It is utilized in national defense support. By requiring high standards, the supplement decreases risk within the supply chain. Increased procurement trust guarantees that only trustworthy products and services are used under defense contracts. This open exposure also makes the process predictable for vendors and the government. Organizations know what they need, and the government knows how to quantify risk.

Who does the DFARS Affect?

Many people and businesses are affected by the DFARS. Government agencies must acquire defense products based on these regulations. Contractors must comply with the rules by part suppliers, technology suppliers, or service suppliers. The supplement covers nearly every step of the procurement process.

For instance, the same requirements have to be met by the firms handling military equipment, software, or cybersecurity. Even those handling non-classified but sensitive data come under its jurisdiction. It encompasses small firms and big corporations also. In short, anyone who’s trying to be a part of defense projects is required to comply with these standards.

Military Equipment

The military hardware is one of the main areas the DFARS oversees. Communication hardware, armored tanks, and aircraft components are all subject to it. As factories make these products, they must be able to prove that every component meets secured standards. History shows that high evaluations reduce risk in missions.

Technology and Cybersecurity

Technology and cybersecurity are the pillars of national defense in today’s world. The DFARS sets worthwhile guidelines for electronic security measures and technical products. The technology vendors are mandated to provide evidence that their products are secure and robust. The regulations mandate elaborate plans to counter cyber threats.

Simple illustrations are computer systems used in secure communication and defense asset management. Organizations must elucidate how they protect networks from penetration. Ongoing audits and upgrading of systems are key compliance factors. There are many examples where compliance to these standards has reduced cybersecurity breaches. This is to maintain robust and secure digital platforms that are required for contemporary defense operations.

Controlled Unclassified Information (CUI)

Controlled Unclassified Information is a sensitive form of information that does not have full classification status but still requires to be handled with care. Rules for handling such information are properly outlined by the Defense Federal Acquisition Regulation Supplement. In most cases, misuse of controlled unclassified information has posed issues. With proper regulations, companies learn how to secure and store information safely.

Practical measures are controlled access storage and strict information-sharing procedures. The majority of companies are now well aware of the need for these measures to avoid vulnerabilities. Rules allow easy management of sensitive information. Provided these rules are followed, information moves securely and smoothly, with operational integrity being preserved.

Conclusion

The DFARS is a significant regulation aimed at strengthening defense procurement. Its standards apply to goods, services, and materials. The regulations maintain fairness, protect public funds, and defend national interests. Contractors and vendors must align their practices to these apparent rules. The supplement is geared towards reducing risk in military gear, technology, and the transmission of sensitive information. For additional details, go to Stanford Chemicals Company (SCC).

Frequently Asked Questions

Q1. Who is required to comply with the Defense Federal Acquisition Regulation Supplement regulations?

A1. Contractors, government organizations, and all defense contractors are required to comply with these regulations.

Q2. What does the DFARS regulate?

A2. It regulates acquisition of military commodities, services, and material with strict regulations.

Q3. How does the DFARS improve cybersecurity?

A3. It adopts strict stipulations which make technology systems safe and less susceptible to cyberattacks.

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What Is Hyaluronic Acid?

First, tell us about this favorite ingredient. Hyaluronic acid (HA) is an acidic mucopolysaccharide, first found and isolated from the cow eye’s vitreous humour. The naturally occurring agent can be seen in the human body, mostly in eyes, knee joint synovial fluid, and skin. HA is crucial in maintaining hydration of the skin, lubricating joints, regulating blood vessel permeability, and healing wounds. As a result of these uses, it is extensively used in skincare, joint therapy, eye drops, and pharmaceuticals.

Why Is Hyaluronic Acid Important?

Research shows that as people age, their ability to produce HA declines. For example, if the level of hyaluronic acid in a 20-year-old is taken as 100%, at the age of 60, it reduces to merely 25%. Not just limited to skin aging and wrinkle formation, but the reduction of hyaluronic acid is also related to age-related changes and conditions in joints, blood vessels, heart, eyes, and brain.[i]

Fig 1. Hyaluronic acid is lost with age

Does Food-grade Hyaluronic Acid Really Benefit Health?

The million-dollar question is whether food-grade hyaluronic acid can be absorbed and utilized by the body. Scientists have diligently endeavored to research this.

One of these studies was carried out by the Mucosal Immunology and Biology Research Center at Massachusetts General Hospital, which is associated with Harvard Medical School. In their study, they analyzed how food-grade hyaluronic acid affects gastrointestinal health. The findings revealed that hyaluronic acid is good for gut health in various ways.[ii]

1. Reducing Intestinal Inflammation & Supporting Gut Health

Hyaluronic acid reduces intestinal inflammation and promotes overall gut health. In the study, mice pre-treated with HA were seen to be protected against colon damage and inflammation induced by Citrobacter rodentium. The mice were also seen to have reduced symptoms of weight loss, rectal bleeding, and diarrhea.

2. Increasing Gut Microbiome Diversity

Mice that received HA exhibited a significant rise in the Simpson Diversity Index, indicating a more diverse and healthier gut microbial population.

3. Strengthening the Gut Barrier Function

Hyaluronic acid improves gut barrier function. The intestinal mucus layer, composed of mucin MUC2 from goblet cells and water and inorganic salts, is a vital protective barrier. Research showed that oral HA augmented goblet cell count and enhanced mucin secretion, thereby enhancing the protection of the gut against infection and injury.

Additional Benefits of Oral Hyaluronic Acid

In addition to gut health, oral hyaluronic acid has also been shown to hydrate skin and reverse aging. A 2017 clinical trial in the Journal of Evidence-Based Complementary and Alternative Medicine followed 20 healthy women aged 45 to 60 who took HA daily for 40 days.[iii] Skin assessments conducted before, during, and after the trial revealed noticeable improvements in elasticity and hydration, along with reductions in roughness and wrinkle depth.

Hyaluronic acid also supports joint health. While HA injections are commonly used to treat osteoarthritis, oral HA has demonstrated positive effects as well. A 2020 study by Hokkaido University, published in the European Journal of Pharmaceutics and Biopharmaceutics, explored how high-molecular-weight HA is broken down by gut microbes into smaller, absorbable fragments. These fragments then enter the lymphatic system and bloodstream, delivering HA to organs and tissues that need it.

Fig 2. The process of food-grade HA being absorbed by the human body[iv]

Conclusion

A number of reputable studies have confirmed that oral HA is not only absorbed by the body but also produces concrete health benefits. With foods containing HA gaining popularity, increasing numbers of consumers are stepping forward with visible positive differences in their skin and overall health. The evidence suggests that the dietary intake of food-grade hyaluronic acid can be a valuable addition to good health and combating the signs of aging.

* Free samples are available. For pricing inquiries, please contact us for a quote: Get A Quote.

[[i]] Feng Ning, Shi Yanli, Guo Fengxian, Guo Xueping. Study on the improvement of skin moisture and antioxidant effect of oral hyaluronic acid in vivo[J]. Food and Drug, 2016, 18(6): 386-390

[[ii]] Mao T, Su CW, Ji Q, Chen CY, Wang R, Vijaya Kumar D, Lan J, Jiao L, Shi HN. Hyaluronan-induced alterations of the gut microbiome protects mice against Citrobacter rodentium infection and intestinal inflammation. Gut Microbes. 2021 Jan-Dec;13(1):1972757. doi: 10.1080/19490976.2021.1972757. PMID: 34592891; PMCID: PMC8489935.

[[iii]] Göllner I, Voss W, von Hehn U, Kammerer S. Ingestion of an Oral Hyaluronan Solution Improves Skin Hydration, Wrinkle Reduction, Elasticity, and Skin Roughness: Results of a Clinical Study. J Evid Based Complementary Altern Med. 2017 Oct;22(4):816-823. doi: 10.1177/2156587217743640. Epub 2017 Dec 4. PMID: 29228816; PMCID: PMC5871318.

[[iv]] Xueli Zheng, Botao Wang, Xin Tang, Bingyong Mao, Qiuxiang Zhang, Tianmeng Zhang, Jianxin Zhao, Shumao Cui, Wei Chen, Absorption, metabolism, and functions of hyaluronic acid and its therapeutic prospects in combination with microorganisms: A review, Carbohydrate Polymers, Volume 299, 2023, 120153, ISSN 0144-8617, https://doi.org/10.1016/j.carbpol.2022.120153.

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