Modified hyaluronic acid with enhanced resistance to degradation

A mild and efficient reduction of negatively charged glucuronate units of hyaluronic acid (HA) into less polar glucose units has not been reported yet. However, this modification could significantly affect physical and chemical properties. Here we show a one-pot procedure where HA is converted into its derivate with carboxyl groups reduced to primary alcohols (HA-Red) without severe polymer degradation. Optimized synthesis aimed at aqueous solutions allowed the preparation of polysaccharides with molecular weights up to 1000 kDa. The chemical structure of HA-Red was proved by 2-dimensional NMR methodologies, FT-IR, LC-MS and SECMALLS. The final materials were exposed to a higher temperature or digested with bovine testicular hyaluronidase (BTH). Obtained data proved higher stability of HA-Red compared to HA, and significant dependence of stability on the degree of modification was observed in most cases. Preliminary in vitro studies showed no negative effects of HA-Red on the growth of 3T3 fibroblasts, which may be promising for applications requiring biodegradable and biocompatible HA derivatives with increased resistance to degradation.