Effect of pH on the Behavior of Hyaluronic Acid in Dilute and Semidilute Aqueous Solutions

Abstract

Summary: Viscosity, asymmetric flow field‐flow fractionation (AFFFF) methods, and dynamic light scattering (DLS) experiments were used to characterize the effect of pH on the behavior of dilute and semidilute aqueous buffered solutions of hyaluronic acid (HA). It is shown that degradation of HA occurs at pH < 4 and pH > 11, and in the domain 4 < pH < 11 virtually no disruption of the HA chains occurs. The pH‐induced scission of HA is attributed to the cleavage of glycosidic bonds. In dilute solutions, intramolecular rupture of HA chains occurs and in the semidilute concentration regime network‐fragmentation is observed at low and high pH values. The degree of degradation of HA is most marked at high pH. From the molecular weight and radius of gyration obtained from AFFFF at different pH values, it is clear that the degradation of HA starts at early times after preparation of the solution, and continues for a couple of days. The kinetics of degradation of HA is fastest at high pH.

Specific ion effects in polysaccharide dispersions

“…In fact, the rheological profiles show that HPO 4 2− increases the viscosity of the SH solution to 77.68 Pa·s, while H 2 PO 4 − lowers (19.75) and PO 4 3− dramatically breaks down the flow curves. We recall that the rheological properties of hyaluronate strongly depend on the pH in a non-linear correlation (Gatej, Popa, & Rinaudo, 2005;Gibbs, Merrill, & Smith, 1968;Gura, Hückel, & Müller, 2003;Maleki, Kjøniksen, & Nyström, 2008). In particular for hyaluronic acid the complex viscosity reaches a maximum value at about pH = 2.5, sided by two remarkable drops in acid (pH = 1.6) and mid-acid conditions (pH = 3.34) (Gatej et al, 2005).…”

“…Moreover, above pH = 12 the viscosity dramatically breaks down, leading to a Newtonian-like behavior. Finally, in a wide range of pH (between 2.8 and 12) the rheological properties and viscosity remain unchanged (Gatej et al, 2005;Maleki, 2008). Furthermore, Maleki investigated the dilute (0.05% w/w) and semi-dilute (0.5% w/w) regimes of HA solutions, with the pH set between 1 and 13 by adding 0.1 M phosphate buffers (Maleki et al, 2008).…”

Phosphate salts facilitate the electrospinning of hyaluronic acid fiber mats

“…The fiber diameter [29,30], number of fiber-fiber contacts [31,32], contact area between fibers [31,33], and fiber-to-fiber bond strength [19,20] have been noted as the most influential parameters on the mechanical properties of randomly oriented nanofibrous mats. In previous work, we have determined that Young's modulus of fiber mats can be greatly affected by the quantity of fiber junctions formed and their interconnectivity [24].…”

“…Maleki et al [20] have shown that when HA is dissolved in solutions at the extreme ends of the pH spectrum (i.e., NaOH:DMF and FA:DMF) the polymer degrades and solution viscosity decreases within 30 min. Therefore, to reduce these degradation effects, electrospinning of HA from neutral solutions is a required step toward unveiling their full potential in future biomedical applications.…”

Hyaluronic Acid in the 3^rd Millennium

“…Since it is hydrophilic, several reactions are performed in aqueous media [145][146][147]: however, they are pH-dependent and, therefore, require acidic or alkaline conditions, which, if too strong, can determine HA degradation [75,145]. Other synthetic methods, involving the use of reagents sensitive to hydrolysis, are performed in anhydrous organic solvents such as dimethylsulfoxide (DMSO) [146] or dimethylformamide (DMF) [148].…”