Hyaluronic acid in Pluronic F-127/F-108 hydrogels for postoperative pain in arthroplasties: Influence on physico-chemical properties and structural requirements for sustained drug-release

Abstract In this study, we reported the hyaluronic acid (HA) on supramolecular structure of Pluronic F-127 (PLF-127) and/or Pluronic F-108 (PLF-127) hydrogels, as well as their effects on release mechanisms, looking forward their application as lidocaine (LDC) drug-delivery systems in arthroplastic surgeries. We have studied the HA-micelle interaction using Dynamic Light Scattering (DLS), the micellization and sol-gel transition processes by Differential Scanning Calorimetry (DSC) and Rheology., of PL-based hydrogels and. The presence of HA provided the formation of larger micellar dimensions from ~26.0 to 42.4 nm. The incorporation of HA did not change the micellization temperatures and stabilized hydrogels rheological properties (G′ > G″), showing no interference on PL-thermoreversible properties. Small-Angle-X-ray Scattering (SAXS) patterns revealed that HA incorporation effects were pronounced for PLF-127 and PLF-108 systems, showing transitions from lamellar to hexagonal phase organization (HA-PLF-127) and structural changes from cubic to gyroid and/or cubic to lamellar. The HA insertion effects were also observed on drug release profiles, since lower LDC release constants (K rel  = 0.24–0.41 mM·h −1 ) were observed for HA-PLF-127, that presented a hexagonal phase organization. Furthermore, the HA-PL systems presented reduced in vitro cytotoxic effects, pointed out their tendency to self-assembly and possible application as drug delivery systems.