Recently, Hyaluronic acid  (HA) has gained considerable attention in rheumatology for its roles in joint lubrication, cartilage preservation, and the modulation of inflammatory and immune responses.  HA is essential for hydration, lubrication, tissue repair, inflammation regulation, and cell signaling. It is synthesized in the plasma membrane of fibroblasts, chondrocytes, and synoviocytes via hyaluronan synthases and various other enzymes.

Hyaluronic acid (HA), or hyaluronan, is an anionic glycosaminoglycan is widely present in various human tissues. This is essential for tissue repair and remodeling, playing a key role in stages of wound healing including inflammation, cell migration, proliferation, and extracellular matrix remodeling. It acts as a structural support and facilitates cell movement during the repair process.

HA helps smooth joint movement and protects cartilage from stress. However, in conditions like osteoarthritis (OA) and rheumatoid arthritis (RA), HA metabolism and distribution are disrupted, impacting joint function.

How HA Helps:

• Lubrication: HA acts as a lubricant in the joints, allowing cartilage to glide smoothly against each other. This helps keep joints healthy and moving freely.
• Shock absorption: HA helps to mitigate the impact on the joint, reducing the risk of damage.
• Pain reduction: HA can help reduce pain, especially when other treatments haven’t worked.
• Cartilage regeneration: HA injections may help regenerate cartilage that has been roughened by osteoarthritis.
• Delaying prosthetic surgery: HA can help delay the need for prosthetic surgery

Role of HA in OA

Safety profile & Adverse effects: HA induces very rarely local reactions or systemic reactions. There is very low incidence of HA related infections and hypersensitivity. In the log term it is safe with low rates of serious adverse events.

HA-based therapies are generally well-tolerated, but careful patient evaluation, appropriate selection, and proper administration are essential to minimize risks.

1. Routes of Administration
2. a) Oral Administration: Intended for systemic effects, oral HA faces challenges such as low bioavailability due to its large size and degradation in thegastrointestinal tract.Limited absorption through the intestinal epithelium hinders the development of effective oral HA formulations.
3. b) Intra-Articular Administration:Commonly used for joint disorderslike OA, this route delivers HA directly into the affected joint. It provides localized relief by reducing pain, improving joint function, and slowing disease progression. Challenges include the need for repeated injections, potential injection-related complications, and rare adverse reactions.
4. Delivery Systems

Various advanced delivery systems have been developed to address HA’s short half-life and poor bioavailability. These systems include:

1. a) Injectable Hydrogels:Provide sustained release and stability for HA.
2. b) Nanoparticles and Micro-Particles:Enhance HA’s stability and targeting capabilities.
3. c) Liposomes: Improve HA delivery and cellular uptake.
4. d) Coatings and Scaffolds:Facilitate targeted delivery and controlled release.

Disease-Modifying Effects and Immunomodulation

HA has the potential to influence disease progression and modulate immune responses in rheumatological disorders. Its therapeutic effects are mediated through interactions with specific receptors, impacts on inflammatory mediators, and modulation of cellular responses. This highlights HA’s role in shaping novel treatment strategies for rheumatic diseases.