Evaluation of the targeting potential of intranasally administered temozolomide controlled-release mucoadhesive multifunctional systems for the treatment of glioblastoma multiforme

• Grant number: 24/19231-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2028
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Alberto Gomes Tavares Junior
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Glioblastoma multiforme is considered the most aggressive type of brain tumor and presents limitations in conventional therapies, due to the difficulty of drugs in crossing the blood-brain barrier (BBB), requiring high doses to obtain the therapeutic effect, and thus contributing to the occurrence of numerous adverse effects. Temozolomide is the gold standard chemotherapy drug for treatment and, although it can cross the BBB in small concentrations when administered orally or intravenously, it has low stability and a short half-life. To overcome these difficulties, the present study seeks to develop multifunctional mucoadhesive systems for intranasal administration of temozolomide, using nanoparticles based on zein, a biocompatible and biodegradable protein that offers a stable matrix for the controlled release of drugs, with the aim of improving drug availability and treatment efficacy. The nanoparticles will be coated with chitosan, a natural cationic polymer with excellent mucoadhesive properties, which increases the residence time of the particles in the nasal mucosa and improves drug absorption. Finally, the nanoparticles will be functionalized with folic acid, which specifically binds to folate receptors overexpressed in tumor cells, including glioblastoma, directing the nanoparticle directly to the target cells. These multifunctional mucoadhesive polymer systems will be characterized physicochemically and their performance will be evaluated by determining the in vitro release profile and ex vivo nasal mucosa permeation, as well as by evaluating in vitro biological assays and the in vivo antitumor assay in an orthotopic glioblastoma model. The proposal innovatively combines a protein and a polysaccharide of natural origin with an active targeting strategy, combined with the use of a functionalizer, aiming at significant improvements in glioblastoma therapy through an alternative administration route. (AU)