Multifunctional Hydrogel Flakes: An Innovative Approach to Localized Delivery of Temozolomide

The multifunctional systems presented here introduce an innovative and deeply thought-out approach to the more effective and safer use of temozolomide (TMZ) in treating glioma. The developed hydrogel-based flakes were designed to address the issues of local GBL therapy, bacterial neuroinfections, and the bleeding control needed during tumor resection. The materials obtained comprise TMZ and vancomycin (VANC) loaded into cyclodextrin/polymeric capsules and embedded into gelatin/hyaluronic acid/chitosan-based hydrogel films cross-linked with genipin. The calcium cations were also incorporated into the systems to facilitate the hemostatic property. That designed formulation was then freeze-dried to serve in flake-like forms, enabling the lining of the surgery site during surgical resection, transferring both TMZ and VANC directly into the surrounding brain parenchyma (the most common site of recurrence). Such a route of drug delivery represents unique features, since systemic side effects are minimized while the drug dose is increased. The developed systems were characterized by their designed functionalities. Therefore, biological evaluation <i>in vitro/ex vivo</i>, antibacterial activity tests <i>in vitro</i>, drug release studies, and physicochemical feature assessments were performed. Our results confirmed that the presented multifunctional long-acting delivery system allows for sustained TMZ release and possesses antimicrobial properties, while simultaneously displaying the hemostatic potential. Overall, we analyzed the unique clinical conditions related to the local CNS drug administration, providing each with dedicated solutions. The presented methods and results describe the invention and its interactions with the environment, an essential step toward clinical application.