Exploring the potential of functionalized nanostructured lipid carriers loaded with cetuximab dispersed in thermo-responsive mucoadhesive hydrogels for the intranasal administration of temozolomide and ellagic acid in the treatment of GBM

• Grant number: 22/11101-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2023
• End date: October 31, 2025
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Jonatas Lobato Duarte
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor, characterized by a high mortality rate and resistance to conventional treatments. Given the complexity of GBM and the blood-brain barrier that limits treatment efficacy, there is an urgent need for innovative therapeutic approaches. The combination of surgical procedures, radiotherapy, and chemotherapy forms the basis of treatment for GBM, but effectiveness is often limited by the tumor's location and treatment resistance. Therefore, it is crucial to develop methods that allow more direct and effective drug delivery. Intranasal administration is a promising route that could enable therapeutic agents to bypass the blood-brain barrier and directly reach the tumor tissue. This project aims to explore the potential of functionalized nanostructured lipid carriers dispersed in thermoresponsive mucoadhesive hydrogels for the co-administration of temozolomide and ellagic acid via intranasal delivery. The focus is to enhance drug delivery efficacy to the brain, improving therapeutic outcomes in GBM treatment. The nanostructured lipid carriers will be synthesized and functionalized with cetuximab, an antibody that inhibits EGFR signaling, a receptor often overexpressed in GBM cells. These carriers will be incorporated into thermoresponsive hydrogels, which are designed to respond to temperature changes, facilitating controlled drug release at the desired site. The formulation will be administered intranasally in animal models of GBM, and effects will be monitored through cell viability analyses, tumor proliferation inhibition, and cellular invasion assessments. Brain samples from treated models will be analyzed to determine the drug's penetration and distribution efficacy. This project represents an innovative approach that combines targeted therapy with a new route of administration, potentially overcoming some significant limitations of traditional GBM treatment methods.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DUARTE, JONATAS LOBATO; DI FILIPPO, LEONARDO DELELLO; VILELLA, KELLE JARCY AZEVEDO; DUTRA, JESSYCA APARECIDA PAES; RIBEIRO, DIEGO MESSALLE; DA SILVA, MONICA FREITAS; DE MEDEIROS, ALEXANDRA IVO; CHORILLI, MARLUS. Chitosan-coated nanoemulsion for intranasal administration increases temozolomide mucosal permeation, cellular uptake, and In vitro cytotoxicity in glioblastoma multiforme cells. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 102, p. 10-pg., 2024-12-01. (14/50928-2, 20/12622-0, 22/11101-1, 21/02609-9)

WALKER, STEPHANIE B.; DUARTE, JONATAS L.; DI FILIPPO, LEONARDO D.; CHORILLI, MARLUS. Improving the Biopharmaceutical Properties of Cannabinoids in Glioblastoma Multiforme Therapy With Nanotechnology: A Drug Delivery Perspective. Drug Development Research, v. 85, n. 8, p. 12-pg., 2024-12-01. (22/11101-1, 20/12622-0)