Functionalized liposomes as a nanocarrier system for enzyme replacement therapy for Fabry disease: pharmacotechnical development and in vitro evaluation

• Grant number: 25/01386-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2025
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria Vitória Lopes Badra Bentley
• Grantee: Luiz Henrique Mesquita Souza
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach, AP.TEM

Abstract

Lysosomal storage diseases represent more than seventy diseases, they are caused by inborn errors of metabolism which, largely due to enzymatic deficiencies, result in a lysosomal accumulation of an undegraded substrate. Fabry disease is part of this group and generates accumulation of glycolipids, especially globotriaosylceramide (Gb3) in lysosomes, caused by a deficiency in the expression of the enzyme ¿-galactosidase A (GLA). Despite affecting different tissues, cardiac complications generate most of the lethality. Currently, its treatment is mainly focused on administering the enzyme intravenously, which improves symptoms, but requires large amounts of enzyme, presents adverse effects and its cellular internalization is very limited. The present project proposes a nanotechnological solution for the targeted delivery of the GLA enzyme, from liposomes functionalized with anti-alpha-7 integrin monoclonal antibodies, a receptor highly expressed in cardiomyocytes, aiming for targeted release and colocalization in lysosomes. The immunoliposomes will be obtained, pharmacotechnically characterized, evaluated for their internalization efficacy in endothelial and muscle cells, colocalization in the lysosome organelle and stability. (AU)