Development of gastro-resistant microspheres containing 5-fluorouracil and genistein for the local treatment of colorectal cancer.

• Grant number: 24/17559-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Fernanda Isadora Boni
• Grantee: Marcos Vinicius Menino
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer is a group of diseases characterized by uncontrolled cellular growth. Globally, there are approximately 14.1 million of new cases each year and about 8.2 million deaths. In Brazil, it is the second leading cause of death, with colorectal cancer being the third most common, exhibiting high incidence and increasing mortality rates. The conventional treatment for this type of cancer, which includes intravenous chemotherapy, faces significant challenges related to systemic side effects and resistance of tumor cells. 5-Fluorouracil (5-FLU) is one of the first-line chemotherapeutics for the treatment of colorectal cancer; however, it has low selectivity and specificity when administered intravenously, leading to severe side effects. Additionally, 5-FLU may have limited efficacy due to vascular obstruction and inefficient neovascularization that occur in solid tumors. Based on that, and considering the severity of colorectal cancer as well as the impacts of conventional therapy on patients' quality of life and treatment efficacy, this project aims to explore the oral administration of 5-FLU in combination with genistein (GEN), a phytosterol with potential antiangiogenic activity. To this end, the development of polymeric micropheres for colon-specific delivery of 5-FLU and GEN is proposed. These micropheres will be rationally designed to exhibit critical attributes of gastric resistance and selective mucoadhesion. The biological behavior will be evaluated using the chicken embryo chorioallantoic membrane model with micro tumor insertion.