Exosome-based delivery of antitumoral drug for targeted glioblastoma therapy

• Grant number: 25/13171-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: February 01, 2027
• End date: January 31, 2028
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Gabriel Lima Barros de Araujo
• Grantee: Carolina Falaschi Saponi
• Supervisor: Helder Almeida Santos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Groningen, Netherlands
• Associated to the scholarship: 24/22372-1 - Development and Advanced Characterization of Nanostructured Delivery Systems for the Enhancement of Glioblastoma Therapy, BP.DD

Abstract

Glioblastoma remains one of the most aggressive and treatment-resistant brain tumors, largely due to the restrictive nature of the blood-brain barrier (BBB) and the limited bioavailability of systemic therapies. Axitinib, a potent VEGF receptor tyrosine kinase inhibitor, shows therapeutic potential for glioblastoma due to its anti-angiogenic properties. However, its clinical application is limited by poor solubility and inadequate accumulation in brain tissues. This project aims to enhance axitinib delivery and efficacy through the development of an exosome-based drug delivery system. Axitinib will be encapsulated within exosomes derived from Raw 264.7 M¿ macrophage exosomes to facilitate targeted delivery across the BBB, ensuring sustained release and reduced off-target effects. Exosome-loaded axitinib will be characterized by therapeutic and loading efficiency, membrane integrity, cellular uptake and biocompatibility. Stability and integrity of the system will be characterized via dynamic light scattering, zeta potential, and transmission electron microscopy. Comprehensive solid-state characterization through preformulation studies will guide the development of the system, with lyophilization ensuring long-term stability. This strategy, aligned with the complementary nanocrystal-based approach developed in the associated direct PhD project, aims to reposition axitinib as a more effective glioblastoma therapy, enhancing tumor accumulation, minimizing toxicity, and maximizing therapeutic efficacy. (AU)