Glioma nanotherapy: Unleashing the synergy of dual-loaded DIM and TMZ

• Published in: International journal of pharmaceutics 2024-11, Vol.665, p.124697, Article 124697
• Main Authors: Sarkar, Sibani, Kumar, Sunny, Saha, Gouranga, Basu, Malini, Ghosh, Mrinal K.
• Format: Article
• Language: English
• Subjects: 3, 3′-Di-indolylmethane (DIM); Blood-brain barrier (BBB); Glioma; Nanotherapy; Synergy; Temozolomide (TMZ)
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124697

Model shows how dual-loaded nanoformulation delivered and works in glioma therapy. Validation for the effectivity of dual-loaded nanoformulations in-vivo in orthotopic glioma model. Delivery of the combination drug treatment would have a better clinical outcome. [Display omitted] Glioblastoma multiforme (GBM) is a highly aggressive form of primary brain tumor in adults, which unfortunately has an abysmal prognosis and poor survival rates. The reason behind the poor success rate of several FDA-approved drug is mainly attributed to insufficient drug distribution to the tumor site across the blood–brain barrier (BBB) and induction of resistance. In this study, we have developed a novel nanotherapeutic approach to achieve our goal. PLGA-based nanoencapsulation of both Temozolomide (TMZ) and EGFR inhibitor 3,3′-diindoyl methane (DIM) in a combinatorial approach enhances the delivery of them together. Their synergistic mode of actions, significantly enhances the cytotoxic effect of TMZ in vitro and in vivo. Moreover, the dual-loaded nanoformulation works more efficiently on DNA damage and apoptosis, resulting in a several-fold reduction in tumor burden in vivo, systemic drug toxicity, and increased survival. These findings suggest the preclinical potential of this new treatment strategy.