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

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release Pub Date : 2025-03-10 DOI:10.1016/j.jconrel.2025.113616

Júlia German-Cortés, Raquel Herrero, Natalia Torroglosa, Alexandra Pumarola, Narine Fischer-Albiol, Sofia Campos-Moreno, Sofia Sabaté, Àngels Alcina, Sandra Mancilla, Belén García, Monserrat Llaguno-Munive, Zamira V. Diaz-Riascos, Cláudia Martins, Simó Schwartz, Roser Ferrer Costa, Ibane Abasolo, Pilar Sánchez-Gomez, Bruno Sarmento, Diana Rafael, Fernanda Andrade

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引用次数: 0

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.

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来源期刊

Journal of Controlled Release 医学-化学综合

CiteScore

18.50

自引率

5.60%

发文量

700

审稿时长

39 days

期刊介绍： The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System. Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries. Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.