Development of in situ gelling delivery system containing mannosylated chitosan nanoparticles for intranasal administration of peptide vaccine

• Grant number: 23/12777-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2025
• End date: July 31, 2027
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Fabiana Testa Moura de Carvalho Vicentini
• Grantee: Camila Machado França de Almeida
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

There is a growing interest in vaccines for intranasal administration due to the advantages of this route in terms of bioavailability, self-administration and because it is a non-invasive route. In addition, for mucosal-associated pathologies, such as mucosal cancer, the intranasal administration contributes to mucosal and systemic immunity. However, the development of an intranasal vaccine encompasses two major challenges: increasing the residence time in the mucosa, in order to reduce the vaccine antigen losses during administration; and stimulation of the immune system. In the case of intranasal vaccine for mucosal cancer, there is a third challenge that is the choice of a tumor antigen against which the immune response will be generated. In this context, this study proposes the development of an in situ gelling delivery system incorporated with mannosylated chitosan nanoparticles to deliver the EGFRvIII peptide as immunotherapy against mucosal cancer. EGFRvIII (variant III of the epidermal growth factor receptor) is a receptor associated with tumorigenicity by increasing cell proliferation and inhibiting apoptosis. As this variant is rarely found in normal tissues, its epitope can be considered tumor-specific, which is the tumor antigen to be used in this study. When associated with mannosylated chitosan nanoparticles, it is expected a better delivery via the mucosa and a greater immunogenic effect of the antigen. The incorporation of this system in the in situ gel aims to favor the applicability of the vaccine and increase the residence time in the nasal route. It is expected with the present project to obtain systems capable of overcoming the main challenges for the administration of intranasal peptide vaccines effectively and safely.