Evaluation of biocompatibility and in vitro antitumor activity of zein nanoparticles intended for the colonic release of 5-fluorouracil and propionate in the treatment of colorectal cancer

• Grant number: 25/00638-2
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: June 21, 2025
• End date: December 20, 2025
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Vitória Ribeiro Mantovanelli
• Supervisor: Joao Conde
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: Universidade Nova de Lisboa, Portugal
• Associated to the scholarship: 24/06447-1 - Colon-specific zein nanoparticles for co-encapsulation of 5-fluorouracil and propionate for potential application in the treatment of colorectal cancer: pharmacotechnical development and in vitro biological activity, BP.MS

Abstract

Colorectal cancer (CRC) ranks third in global cancer-related deaths and is one of the five most commonly diagnosed types of cancer worldwide. 5-fluorouracil (5-FLU) is the drug of choice for the treatment of CRC; however, it presents unstable absorption in the gastrointestinal tract (GIT), problems related to its high hydrophilicity, short plasma half-life, and variation in its pharmacokinetics, causing adverse effects. The colon-specific release of 5-FLU from polymeric nanoparticles has been explored in the literature through the development of delivery systems for oral administration. In addition, the co-encapsulation with propionate in zein nanoparticles could increase the efficacy of the therapy. Propionate is a short-chain fatty acid, a postbiotic with beneficial actions for the health of the intestinal microbiota and the host. Although the combination of nanotechnology represents a promising strategy, its translation to the clinic has been hampered by the lack of models that provide reliable and predictive knowledge about the efficiency of these formulations. However, the use of in vitro cellular models constitutes a promising tool to evaluate the biocompatibility of these nanoparticles, in addition to providing predictive results on antitumor activity. Based on the above, the present study aims to perform in vitro biocompatibility analysis in 2D and 3D models, in addition to evaluating the antitumor properties of zein-based nanoparticles containing 5-FLU and propionate, to be carried out at Universidade Nova de Lisboa, under the supervision of Prof. Dr. João Conde.