Hyaluronic Acid

Hyaluronic acid is a non-sulfated glycosaminoglycan, a high molecular weight negatively charged polymer composed of monosaccharides connected by alternating β-1, 4 or β-1, 3 glycosidic bonds. It has physical and chemical properties such as hydrophilicity, biocompatibility, biodegradability, and non-toxicity. Hyaluronic acid binds to specific extracellular cell receptors, including CD44, hyaluronic acid-mediated motility receptors, Toll-like receptor 2, Toll-like receptor 4, lymphatic endothelial hyaluronic acid receptor 1, etc. Among them, CD44 is a glycoprotein receptor that participates in various signaling pathways, participates in angiogenesis and wound repair, and is significantly highly expressed on the surface of activated macrophages and cancer cells. In recent years, hyaluronic acid has received widespread attention as an ideal carrier in the field of nanomedicine. In 2007, researchers first prepared nanoparticles containing hyaluronic acid, which were 200~500 nm in size and were used to encapsulate small interfering RNA to achieve specific delivery in cells. Later, researchers also found that nanoparticles containing hyaluronic acid have good biocompatibility and macrophage targeting ability. Therefore, for inflammatory diseases, the binding of hyaluronic acid to CD44 on the surface of activated macrophages can be used to give nanoparticles targeting ability and improve the targeted drug delivery ability.

Figure 1. Hyaluronic acid-based nanosystems for drug delivery. (Sylvia N. Kłodzińska, et al.; 2021)

Systemic drug delivery often faces many challenges, including rapid renal clearance, inability to target specific tissues, and poor water solubility of small molecule drugs. The use of hyaluronic acid-containing nanoparticles as drug delivery systems has significant advantages such as good biocompatibility, low toxicity, and stability. 1. Good biocompatibility: The hydrophilic hyaluronic acid shell has the ability to translocate across biological barriers, allowing the drug to completely enter target cells, tissues and organs through the intracellular and intracellular barriers, and prolong the action time of the drug; 2. Low toxicity: After the surface is coated with hyaluronic acid, the immunogenicity of the nanoparticles is extremely low. After entering the body, it will basically not produce an immune response or cause immune damage, and the liver toxicity and kidney toxicity are minimal; 3. Stability: Hyaluronic acid The acid shell makes the nanoparticles negatively charged, which is beneficial to the suspension of the nanoparticles in the solution, avoids aggregation and precipitation, and avoids binding to serum proteins, effectively prevents the drug from being degraded during transportation, is beneficial to extending the plasma half-life, and can Delivered in a sustained and controlled manner; 4. Targeting: hyaluronic acid specifically binds to the CD44 receptor on the surface of macrophages or cancer cells, providing targeting ability for nanoparticles; 5. Degradability: widely present in tissues Hyaluronic acid degrading enzyme. After the hyaluronic acid layer wrapped on the surface enters the inflammatory tissue, it can be degraded by the hyaluronic acid degrading enzyme in the tissue, allowing the internally wrapped drugs, molecules and RNA to be fully released into the tissue to play a role; 6. Convenience: The smallest capillary diameter is about 2~3 μm, and the size of nanoparticles is generally 150~250nm. It will not cause microvascular blockage and allows intravenous administration; 7. Visual therapy: Nanoparticles can carry tracers as needed. It is a good bioimaging agent that can be used in positron emission tomography and magnetic resonance imaging, which is helpful for observing the degree of tissue inflammation and judging the efficacy of drugs. Although hyaluronic acid is used to prepare nanoparticles due to its high stability and low toxicity and other physical and chemical properties, and is intended to be used for the treatment of various diseases, the current preparation of hyaluronic acid nanoparticles requires the molecular weight, particle diameter and There is still no standard for surface charge. Preparing such combined nanoparticles is complicated, has low industrial feasibility, and is difficult to apply in clinical applications. Hyaluronic acid nanoparticles with different molecular weights have different pharmacokinetics, tissue distribution, dosage regimens and drug efficacy, and there is still a lack of relevant research. Therefore, we provide polymers for making hyaluronic acid nano drug delivery systems to promote research in this field.

Alternate Names:
Hyaluronan
Hyaluronate
Sodium hyaluronate
Glycosaminoglycan
HA

References:
1. Sylvia N. Kłodzińska, et al.; Biopolymer-Based Nanomaterials in Drug Delivery and Biomedical Applications. Chapter 9 - Hyaluronic acid-based nanosystems for drug delivery applications. ACADEMIC PRESS. 2021, Pages 221-250.

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