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Hyaluronic Acid

Updated: Jun 4, 2020

Hyaluronic acid (HA) is well-known for the benefits it provides in topical formulations, including moisturi­zation, delivery of water and actives to the skin, film formation and antioxidant effects.

HA also is critical to the functional well-being of normal physiological processes of the skin; notably protection via said antioxidant effects, hydration, stabilization of the tissue matrix structure and cellular repair.

Its linear structure consists of repeating dimers of N-acetyl glucosamine and Na-D-glucuronate, which are linked together to form a long, unbranched chain having a high molecular weight (HMW) of 2-4 ×106 Da.

HMW HA chains form hydrated random coils, which interact to produce highly viscoleastic solutions.

To enhance the beneficial properties of topical HMW HA and increase its function­ality, stability and use, derivatives were developed using divinyl sulfone as a cross-linker to react with HA’s primary hydroxyl groups and covalently bond the chains together via sulfonyl-bis-ethyl cross-links.

Using this approach, the backbone of the HA chain remains unchanged, which allows the formation of soft, viscoelastic hydrated gels that maintain the biocompa­tibility of the HA molecule.

Such cross-linked HA gelsa were developed first for use in medical devices as soft tissue augmentation agents, to correct soft tissue deformities, e.g., facial wrinkles, via intradermal injection; they therefore have been established as safe and biocompa­tible.

A unique feature of these cross-linked HA gel matrices is the ability to form “nonequi­librium” or non-fully swollen gels with a range of concentr­ations and rheological parameters that are effective delivery vehicles for different actives.

This property is a direct result of their structure and water-binding capacity. Non-equilibrium gels are typically better able to incorporate and entrap actives, as they may be further swollen in the presence of a solution of the active. The actives therefore become part of the hydrated molecular cage of the cross-linked HA gel.

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