March 13, 2025 - Baltimore, MD 21205, USA
In the world of medicine, drug delivery systems are crucial. It can make drugs bioavailable, less side-effect and more therapeutically efficient, by rationally planning and optimising drug release, site and control. Targeted delivery systems, for instance, allow us to release medicines precisely where disease is present, so that normal tissues are less affected, treatments are more effective, and toxic and side effects are reduced.
Biocompatibility and targeted delivery are two major considerations in drug development. Biocompatibility – the drug carrier material will not elicit an immune or toxic reaction in the body and the drug will be released safely and efficiently in the body. Targeted delivery allows for the right drugs to reach the right target cells or tissues using molecular recognition thereby optimizing the therapy and minimizing adverse effects.
The natural biomolecules mainly responsible for the delivery of drugs include Chondroitin Sulfate and Hyaluronic Acid. Chondroitin sulfate is a polysaccharide that is easily biocompatibility and biodegradable. We use it mostly for synthesising drug delivery vehicles such as nanoparticles and composites that can carry drugs in sustained release and tailored way. We also use it to render the drugs soluble and stable, for absorption. It is hydrophilic, and so carries drugs into the body easily. Not only can Hyaluronic acid make the drug more bioavailable, but it can make the drug more permeable in the tissue, and hence the drug work better. Hyaluronic acid can also be co-created with other biomolecules to form composites for more complex drug delivery.
Chondroitin sulphate and hyaluronic acid not only make drugs biocompatible and targetable; they provide new channels for better therapy. These biomolecules opened up possibilities for today's medicine and created technology to deliver drugs.
CS is the animal's glycosaminoglycan, and it's existed in cartilage, skin, blood vessels and joints. It consists of N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcA) connected side by side, through -1,4 glycosidic bonds. Every repeating unit has a sulfate group and the number and location of sulfate groups matters a great deal to chondroitin sulphate biology.
Chondroitin sulfate affects multiple system in biology: Anti-inflammatory, Antioxidant, cell proliferation promotion, and tumor cell growth inhibition.. Because it inhibits the NF-B system, reduces the production of inflammatory factors, and regulates the Wnt/-catenin system. And chondroitin sulphate (which mimics heparin and cell growth in smooth muscle cells) combine with fibroblast growth factor (bFGF), which also promotes cell growth.
What uses chondroitin sulfate in drug delivery are principally related to its role as a carrier. Because it is highly biocompatible and designable, chondroitin sulfate is often used to make nanoparticles, microspheres and other nanocarriers for better bioavailability and drug targeting. For instance, chondroitin sulfate can be melded with medicines like rhein to produce tumour-directed nanoparticles for cancer therapy.
The cartilage-specific delivery of drugs is also very promising for chondroitin sulfate. When bonded with solid lipid nanoparticles or with other bioactive molecules, chondroitin sulfate delivers drugs directly to the cartilage tissue in a precise way, for sustained release and tissue-targeting. This is a property that can be especially useful in treating osteoarthritis and rheumatoid arthritis, because it targets chondrocytes, inhibits inflammation and heals cartilage.
Chondroitin sulfate offers many opportunities in the delivery of drugs due to its specific chemical composition and biological functions. Not only can it be a carrier drug to enable stable and bioavailable drug but also provide tissue-specific treatment with targeted delivery mechanism, and hence has huge promise for osteoarthritis, rheumatoid arthritis, and cancer.
HA is a natural polysaccharide, high molecular weight and complex. It's ubiquitous in the human tissues: joint fluid, synovial fluid and the airways. Its chemistry is made up of alternated D-glucuronic acid and N-acetylglucosamine. That special molecular configuration confers on HA all kinds of key biological properties, from regulating extracellular matrix stability to the water-holding capacity of tissues.
Hyaluronic acid also helps keep tissues hydrated and heal wounds. It controls cell proliferation, differentiation and migration by binding to receptors on the surface of cells, which results in wound healing and angiogenesis. HA can also soak up a great deal of water to create a thick solution that keeps tissues well-watered and gives cells a living milieu.
In the drug delivery, HA is a very common solution as it is very biocompatible, biodegradable and non-immunogenic. Hyaluronic acid is a drug carrier that delivers drugs to target tissues or cells using passive or active targeting. For instance, in cancer therapies, hyaluronic acid can be directed at cancer cells with CD44 receptors, which increases the bioavailability and therapeutic effectiveness of medicines. Furthermore, hyaluronic acid can also be used to regulate drug release, and if the physicochemical composition (ie, molecular weight and concentration) of the it is controlled, then long-term or rapid drug release can be achieved. Hyaluronic acid is biocompatible and biodegradable which makes it a perfect drug delivery material. It can be broken down into a non-toxic smallmolecule by the body's enzymes, and hence free of the toxicity threats that will accompany long-term storage. This is the feature that gives hyaluronic acid wide applications in ophthalmology, skin care and tissue engineering.
We apply hyaluronic acid in all kinds of treatments. In the eye-care space, for example, hyaluronic acid is used as a medication in dry eye and cataract surgery; in the skin industry, hyaluronic acid is used in moisturisers and anti-ageing creams; and in the field of cancer, hyaluronic acid as a carrier can enhance the ability to target and treat cancer drugs. In addition, hyaluronic acid is also used in osteoarthritis and tissue regeneration therapy for pain relief via joint lubrication and cartilage restoration. By all measures, hyaluronic acid was chemically and biologically flexible when it came to delivering drugs. It is very biocompatible and biodegradable, so a valuable tool for both medical research and clinical use – particularly for tissue engineering, oncology and wound healing.
High stability: Chondroitin sulfate is viscoelastic, and it can also prevent drugs from being disintegrating by proteolytic enzymes. The non-sulfated glycosaminoglycan hyaluronic acid, however, is very water absorption and water-locked to help keep medications more solubilised and stable.
Figure 1. A schematic illustration of the concept of injectable CS-CHO/HA-SH hydrogel formation.(Johnson M, et al.; 2024)
Controlled release: If you combine chondroitin sulfate and hyaluronic acid, the structure and chemistry of both would be made stable release of drug. Chondroitin sulphate, for instance, might adhere drugs via electrostatic attraction; hyaluronic acid would control how much of the drug was released by molecular shape.
Joint targeted: Both chondroitin sulfate and hyaluronic acid support articular cartilage. Chondroitin sulphate inhibits inflammatory molecules and supports the growth and differentiation of chondrocytes, while hyaluronic acid smooths and repairs joint function by resealing synovial fluid. That is what better heals articular cartilage.
Skin care: Chondroitin sulfate tames inflammation with anti-inflammatory action and hyaluronic acid provides a balance of skin wellness by adhering moisture to the skin through moisture.
Chondroitin sulfate and hyaluronic acid together not only enhance drug stability and release control, they increase the drugs biological efficacy by synergy. For instance, in the treatment of osteoarthritis, this trio can substantially reduce the production of inflammatory factors and increase chondrocyte growth and differentiation, which will help the body to regain the function of its joints much faster.
Chondroitin sulfate and hyaluronic acid are both biocompatible and safe so when used together, they decrease toxicity and adverse effects of the drugs. Moreover, this combination prevents the systemic side effects by suppressing the distribution of drug in non-target tissues via targeting.
This bifunctional structure can be a multifunctional drug carrier to achieve dual targeting. For instance, in osteoarthritis, chondroitin sulfate can activate the CD44 receptor in chondrocytes and hyaluronic acid acts on the joint cavity with its lubricating effects – this does two things. Chondroitin sulfate and hyaluronic acid have strong interplay in drug delivery for both enhanced stability and control of release as well as therapeutic effects and reduced side effects. This dual-function mechanism gives the developers new ideas to build new multifunctional drug carriers.
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