Development and Advanced Characterization of Nanostructured Delivery Systems for the Enhancement of Glioblastoma Therapy

• Grant number: 24/22372-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2025
• End date: May 31, 2029
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Gabriel Lima Barros de Araujo
• Grantee: Carolina Falaschi Saponi
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Oncological drugs often face challenges such low solubility and poor bioavailability, leading to higher required doses, increased systemic toxicity, and adverse effects. Axitinib, a potent tyrosine kinase inhibitor targeting VEGF receptors, shows promising potential for glioblastoma treatment due to its anti-angiogenic properties. However, its therapeutic performance in brain tumors is hindered by poor solubility and limited bioavailability, which restrict the concentration of the drug that reaches the tumor site. Additionally, the blood-brain barrier (BBB) hinders effective drug accumulation at the tumor site.This project aims to enhance axitinib's bioavailability and efficacy in glioblastomas by developing and characterizing optimized nanostructured delivery systems. Two platforms-nanocrystals and exosome-based systems-will be employed. Axitinib nanocrystals, produced through high-energy milling, improve solubility and dissolution, boosting systemic absorption and drug concentration at the tumor site. In parallel, axitinib will be encapsulated within hCMEC/D3-derived exosomes to facilitate targeted delivery across the BBB, ensuring sustained release and reduced off-target effects. Stability and integrity of both systems 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 both systems, with lyophilization ensuring long-term stability. Exosome-loaded axitinib will be also characterized by therapeutic and loading efficiency, membrane integrity, cellular uptake and biocompatibility. This strategy aims to reposition axitinib as a more effective glioblastoma therapy, enhancing tumor accumulation, minimizing toxicity, and maximizing therapeutic efficacy.