P07.07.A A NEW SOL-GEL DERIVED DRUG DELIVERY SYSTEM FOR THE LOCAL TREATMENT OF GLIOBLASTOMA BASED ON FULLY RESORBABLE RENACER FIBER FLEECES

Abstract BACKGROUND Glioblastoma (GBM) remains difficult to treat due to its invasive growth, molecular heterogeneity, and therapy resistance. Tumor recurrence at the resection margins represents a key clinical challenge, as standard postoperative chemotherapy often fails at this site. This study aims to prevent local recurrence by applying a drug-loaded silica-based fleece (RENACER®) to the resection cavity. The material degrades into ortho-silicic acid (oSA). MATERIAL AND METHODS The fleece was synthesized via sol-gel processing and produced by pressure spinning, electrospinning, or both. One hydrophilic and one hydrophobic drug were embedded within the fiber matrix. Structural and mechanical properties were characterized (microscopy, tensile testing, NMR), and cytotoxicity was tested according to DIN-EN-ISO-10993-5. Drug release was quantified by high performance liquid chromatography (HPLC), and efficacy on cellular level was evaluated using xCELLigence, alamarBlue™, and microscopy in vitro and ex vivo. RESULTS Pressure spinning yielded microfibers (46.1 ± 5.1 µm), while electrospinning produced submicrofibers (0.9 ± 0.2 µm). Drug-free fibers showed no cytotoxicity in eluate or direct contact assays (cell viability > 80 %). Mechanical flexibility (24 to 0 mm diameter at break), delamination, and degradation (7-35 days to complete oSA release) could be tuned via synthesis parameters. Structure-property relationships were established across fabrication methods. Drug release studies confirmed full release of both agents and demonstrated modulated dual kinetics depending on fiber diameter and drug properties. The dual drug release and its efficacy against GBM cells was confirmed through various cell health assays in vitro (U87, U138, GaMG and 9L/lacZ) and on ex vivo patient-derived organoids. Real-time monitoring on GBM cell lines demonstrated controlled drug release. Moreover, treatment of ex vivo organoids with our fleece led to a significant reduction in both tumor size and viability. CONCLUSION We developed a local drug delivery system for GBM recurrence, combining two spinning techniques and integrating dual-drug release. The approach showed effective cytotoxicity in vitro and ex vivo and offers a tunable platform for postoperative therapy.