Preclinical evaluation of several polymeric micelles identifies Soluplus®-docetaxel as the most effective candidate in multiple glioblastoma models.

Glioblastoma multiforme (GBM) is one of the most lethal cancers, with limited treatment options due to the blood-brain barrier (BBB), systemic toxicity, and treatment resistance. Nanomedicine offers potential solutions to these challenges. This study explores Pluronic® F127 and Soluplus®-based micelles as carriers for Lomustine, Gefitinib, and Docetaxel to determine the optimal system for GBM therapy. Micelles were physicochemically characterized and biologically validated using U87-MG and U251-MG GBM cell lines in 2D and 3D models, assessing internalization, safety, and therapeutic efficacy. Soluplus® micelles (SM) showed favorable properties for intravenous administration, including low polydispersity, efficient drug release in the tumoral microenvironment, minimal cell toxicity, and a BBB-crossing rate of 15 %. Among the drugs tested, Docetaxel showed the lowest IC values in both 2D cell models and demonstrated superior efficacy in 3D cultures when delivered by SM. Molecular analysis confirmed that SM-D impacts key GBM-related pathways, affecting markers like E-cadherin, EPCAM, L1CAM, or EGFR. In vivo, SM-D significantly reduced tumor mass and cancer cell density, showing a favorable safety profile compared to free Docetaxel, as evidenced by reduced weight loss and histological assessments. Overall, SM-D stands out as the most promising approach for GBM treatment, supporting the potential of nanomedicine in overcoming the barriers to effective glioblastoma therapy.