Effect of a Hyaluronic acid amide derivative on equine synovial fluid viscoelasticity

A novel amphiphilic hyaluronic acid (HA) derivative has been obtained by the amidation of the carboxylic group of the glucuronic acid with hexadecylamine. This derivative, HYADD4®-G, is the hexadecylamide of 500-730 kDa hyaluronic acid, derived from Streptococcus equi and at 2% degree of substitution ( 2 moles hexadecylamine per 100 moles hexuronic acid) . Its viscoelastic properties at a concentration of 5 mg\ml in phosphate buffer saline, have been compared to those of solutions of native HA of the same molecular weight and in particular the changes in the viscoelastic properties of equine synovial fluid after the addition of different volumes of HYADD®4-G (viz, ratios synovial fluid:HYADD®4-G of 1:2, 1:1, 3:1, 7:1) have been evaluated. In the frequency range 0.1-10 Hz, the rheological behaviour of HYADD®4-G is typical of a weak gel. Throughout the whole frequency range, the elastic modulus G’ is higher than the viscous modulus G,” and both moduli are frequency independent. The elastic modulus is about two orders of magnitude higher than that of a comparable solution of native HA. The HYADD®4-G elastic modulus, ranges from 40 to 100 Pas, and its viscous modulus from 8-12 Pa.s The addition of HYADD4®-G to equine synovial fluid (SF) increased its viscolelasticity at all the SF:HYADD®4-G ratios tested, and after 48 hours at 37°C the viscoelasticity values are reduced by ca 50-70% . These results demonstrate that HYADD®4-G is able to integrate with SF, increasing the synovial fluid rheology, and could be an interesting new option in viscosupplement therapy of osteoarthritis, particularly considering its low degree of chemical modification from native hyaluronic acid.