Influence of hyaluronic acid and sodium alginate on the rheology and simvastatin delivery in Pluronic-based thermosensitive injectable hydrogels

The use of injectable materials is an attractive alternative for medical treatments because it does not require surgical intervention serving as a matrix that supports and entraps drugs, and the rheological characterization is necessary to ensure safe conditions of its application in an organism. Simvastatin (SIM) was chosen to compose the formulations due to its osteopromotive properties. Therefore, this study aimed to choose two formulations based on Pluronic F127, that is thermosensitive in aqueous solutions and SIM, one containing hyaluronic acid (HA) and the other sodium alginate (SA), and to verify the influence of different SIM concentrations on the rheology of hydrogels and their release behavior in the presence of these natural polymers. The methodology was based on rheological tests to modulate gelation, thermal analysis, hydrogel characterizations and in vitro release tests. Analysis of gelation temperatures revealed that adding SIM up to 5.0 wt % minimally affect the viscosity of the hydrogels, whereas by adding natural polymers increased the viscosity at 20 °C without affecting the viscosity at 37 °C. The compositions 18%F127/5%SIM/0.25%HA and 18%F127/5%SIM/0.5%SA were chosen as optimal. The drug release results showed that the addition of natural polymers delayed SIM delivery, with better results for the HA hydrogel. After 240 h, the HA hydrogel released 64% of SIM, whereas the SA hydrogel released 85%. The results showed that the presence of SIM does not interfere with the rheology of the hydrogels and that they exhibit modified drug-release kinetics, making them promising formulations for use as injectables.