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

• Grant number: 24/06447-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2024
• Status: Discontinued
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Vitória Ribeiro Mantovanelli
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 25/00638-2 - 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, BE.EP.MS

Abstract

Colorectal cancer (CRC) ranks third in terms of global cancer-related deaths, being one of the five most diagnosed types of cancer worldwide. The therapeutic management of this condition must be carried out under careful analysis since currently, available therapeutic measures can negatively impact the patient's quality of life. 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 many adverse effects. The colon-specific release of 5-FLU from polymeric nanoparticles, aiming at efficacy and reduction of side effects, lower dose of the drug, improvement in therapeutic efficacy, and greater stability of active ingredients has been explored in the literature through the development of release systems for oral administration. Among the natural materials used for delivery to the colon, zein, a water-insoluble corn protein with high biosafety, has gained increasing prominence. In addition to its biocompatibility and low toxicity, zein can resist degradation caused by gastric acid and gastrointestinal enzymes. Additionally, the co-encapsulation of 5-FLU with propionate in zein nanoparticles could increase the effectiveness of the therapy. Propionate is a short-chain fatty acid, produced naturally in the gastrointestinal tract through the fermentation process of dietary fiber, acting as a postbiotic with beneficial actions for the health of the intestinal microbiota and the host. Based on the above, the present work aims to develop zein-based nanoparticles for the colon-specific release of 5-FLU and propionate to evaluate the potential application in treating CRC.