Combining Ultra-High Drug-Loaded Micelles and Injectable Hydrogel Drug Depots for Prolonged Drug Release
Hydrogel-based drug depot formulations are of great interest for therapeutic applications. While the biological activity of such drug depots is often characterized well, the influence of incorporated drug or drug-loaded micelles on the gelation properties of the hydrogel matrix is less investigated. However, the latter is of great importance from fundamental and application points of view as it informs on the physicochemical interactions of drugs and water-swollen polymer networks and it determines injectability, depot stability, as well as drug-release kinetics. Here, the impact of incorporated drug, neat polymer micelles, and drug-loaded micelles on the viscoelastic properties of a cytocompatible hydrogel is investigated systematically. To challenge the hydrogel with regard to the desired application as injectable drug depot, curcumin (CUR) is chosen as a model compound due to its very low-water solubility and limited stability. CUR is either directly solubilized by the hydrogel or pre-incorporated into polymer micelles. Interference of CUR with the temperature-induced gelation process can be suppressed by pre-incorporation into polymer micelles forming a binary drug delivery system. Drug release from a collagen matrix is studied in a trans-well setup. Compared to direct injection of drug formulations, the hydrogel-based systems show improved and extended drug release over 10 weeks.