Hydrodynamic Compatibility of Hyaluronic Acid and Tamarind Seed Polysaccharide as Ocular Mucin Supplements

Hyaluronic acid (HA) has been commonly used in eyedrop formulations due to its viscous lubricating properties even at low concentration, acting as a supplement for ocular mucin (principally MUC5AC) which diminishes with aging in a condition known as Keratoconjunctivitis sicca or dry eye. A difficulty has been its short residence time on ocular surfaces due to ocular clearance mechanisms which remove the polysaccharide almost immediately. To prolong its retention time, tamarind seed gum polysaccharide (TSP) is mixed as a helper biopolymer with HA. Here we look at the hydrodynamic characteristics of HA and TSP (weight average molar mass M-w and viscosity eta) and then explore the compatibility of these polymers, including the possibility of potentially harmful aggregation effects. The research is based on a novel combination of three methods: sedimentation velocity in the analytical ultracentrifuge (SV-AUC), size-exclusion chromatography coupled to multiangle light scattering (SEC-MALS) and capillary viscometry. HA and TSP were found to have Mw=(680 +/- 30) kg/mol and (830 +/- 30) kg/mol respectively, and eta=1475 +/- 30 ml/g and 675 +/- 20 ml/g, respectively. The structure of HA ranges from a rodlike molecule at lower molar masses changing to a random coil for M-w > 800 kg/mol, based on the Mark-Houwink-Kuhn-Sakurada (MHKS) coefficient. TSP, by contrast, is a random coil across the range of molar masses. For the mixed HA-TSP systems, SEC-MALS indicates a weak interaction. However, sedimentation coefficient (s) distributions obtained from SV-AUC measurements together with intrinsic viscosity demonstrated no evidence of any significant aggregation phenomenon, reassuring in terms of eye-drop formulation technology involving these substances.