Development of enzymatically crosslinked natural deep eutectogels: versatile gels for enhanced drug delivery

Injectable hydrogels have been extensively studied due to their minimally invasive properties, ease of application, and void-filling properties. In this work, we tested the possibility to prepare a new type of gels, so called eutectogels, where water is replaced by a natural deep eutectic system (NADES), conferring it longer stability. Eutectogels based on betaine : glycerol 1 : 2, were prepared by enzymatic mediated crosslinking, using horseradish peroxidase (HRP) as catalyst and gelatine-phenol conjugated polymer. In comparison to hydrogels, that required higher enzyme concentration (15 U mL −1 ) to have gelation time under 2 minutes, the eutectogels were obtained using 10 and 5 U mL −1 of HRP, with gelation times of 30 and 50 seconds, respectively. Finally, ketoprofen was loaded into the polymeric matrix, and release studies were conducted. The presence of NADES was essential for the formulation of the drug loaded gel, which was able to release up to 70% of the drug within 10 days, therefore, it was possible to conclude that these eutectogels work as matrix for the controlled delivery of ketoprofen in aqueous medium. The in vitro biological evaluation of the individual components of the eutectogel support no cytotoxic effect, an early indication of potential biocompatibility. We propose a new injectable eutectogel prepared by enzymatic crosslinking, using NADES, betaine : glycerol (2 : 1), as solvent. The potential of using this material with improved rheological properties as drug delivery system, has also been evaluated.