Controlled release of a model protein drug ovalbumin from thiolated hyaluronic acid matrix

The objectives of this work were to investigate the properties of the thiolated hyaluronic acid (HA) with different molecular weights (MWs) and to assess the effects of MW and dissolution medium on the release of ovalbumin from thiolated HA matrix tablets. Four HA-cysteine (HA-Cys) conjugates with increasing MWs (47, 101, 260 and 550 kDa) were synthesized. The resulting HA-Cys conjugates exhibited increased stability against hyaluronidase degradation, and such an effect became stronger with the increase of polymer MW. Swelling and erosion studies of HAs or HA-Cys conjugates based matrix tablets were performed in various media. We found that the water uptake capacity and erosion rate were strongly dependent on MW of HA, ionic strength and pH of the medium. Release studies showed that all investigated factors exerted effects on the drug release. Most of the release data based on HA matrix tablets followed super Case II transport but conformed to non-Fickian diffusion with HA-Cys conjugates. Taken together, this work managed to develop HA-Cys conjugates-based matrix tablets as controlled release systems for protein with tunable release rate through varying MWs of polymer.