Differences among Three Branded Formulations of Hyaluronic Acid: Data from Environmental Scanning Electron Microscope Profile, Rheology Behavior and Biological Activity

Background: This study has analysed the viscosupplemental proprieties of three commercially available formulations of Hyaluronic Acid (HA) suspension (F1: Synvisc, Hylan G-F 20; F2: Hyalgan; F3: Donegal HA 2.0), which differ in composition, Molecular Weight (MW) and HA content. Methods: Analyses were conducted using rheology measurements and Environmental Scanning Electron Microscope (ESEM). The capacity of the three tested formulations to inhibit specific Metalloproteases (MMPs) was also evaluated. Results: F1 is the only sample showing viscoelastic properties but may have increased immunogenicity attributable to the subsequent chemical cross-linking process that enhances the MW. F2 and F3 show a lower viscosity compared to F1. F2 has the lowest viscosity at low shear rate, the lower independence from the oscillatory stress and a solution-like rheology behaviour. F3 display a solution behaviour. However, unlike F2, F3 crossover point falls in the middle of the frequency range of interest showing a considerable rheological behaviour. The internal structure of F3 (pseudo-spongy thick filaments) suggests that it has the ability to interact with a great water content. The crossover points of the examined samples clearly reveal their different rheological behaviour, allowing their classification in gel-like or solution-like materials. F3 has higher ability in inhibiting MMP- 2 and MMP-9 activity compared to F1 and F2, probably due to its specific MW and/or higher HA concentration. Conclusion: The three tested HA formulations differ in rheological properties and inhibition of MMP-2 and MMP-9 activity. F3 seems to be the most appropriate formulation for the treatment of osteoarthritis and rheumatoid arthritis.