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.