A Hyaluronic Acid-Based Formulation with Simultaneous Local Drug Delivery and Antioxidant Ability for Active Viscosupplementation

[Image: see text] Hyaluronic acid (HA) and its derivatives are widely used for intra-articular injection to augment compromised viscoelastic properties of damaged synovial fluid. Combining HA-based devices with anti-inflammatory drugs or bioactive principles in order to provide an additional benefit to the viscosupplementation is emerging as a new promising approach to improve the clinical outcome. Here, we aim to design a novel active viscosupplementation agent that can load and release hydrophobic drugs and at the same time possessing antioxidant properties. Optimized ternary systems named HCV based on HA, (2-hydroxypropyl)-β-cyclodextrin (CD), and vitamin E (VE), without being engaged in formal chemical bonding with each other, showed the best viscoelastic and lubrication properties along with antioxidant capabilities, able to solubilize and release DF. The physical–chemical characterization suggested that the HCV system displayed rheological synergism and higher thermal stability because of the presence of VE and its antioxidant activity, and the loading of hydrophobic drugs was improved by the presence of CD and VE. Cell morphology and viability tests on L929 cells exhibited high biocompatibility of the HCV system with higher level expression of anti-inflammatory interleukin-10.