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

Abstract

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 IC₅₀ 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.