Preparation and evaluation of oral nanocarriers of 5-fluorouracil and intestinal metabolics

• Grant number: 19/03241-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2020
• End date: March 31, 2023
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Luciana Biagini Lopes
• Grantee: Claudio Fukumori
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors, AP.JP2

Abstract

Colorectal cancer (CRC) is one of the most common in the world and its chemotherapeutic treatment is considered aggressive due of the several adverse effects observed, which include those for the first-choice drug: 5-fluorouracil (5-fu). As a result of its low oral bioavailability and short plasma half-life, this drug is administered intravenously at high dosage and frequency, which, combined with the fact that it is not selective for tumor cells, leads to serious adverse effects and limits the patient quality of life. Here, we propose to use a nanotechnology approach for oral administration of 5-fu to increase its concentration at the desired site. Considering that short chain fatty acids (SCFA), which are available in the large intestine as a result of fiber fermentation by the intestinal microbiota, have effects on CRC, we propose the co-encapsulation of SCFA-triglycerides along with 5-fu in order to boost the drug effect. This would allow the dose to be reduced to reach the same therapeutic effect, and therefore, produce less systemic adverse effects. We will study two nanocarrier systems: multiple nanoemulsion and nanostructured hybrid lipid-polymer carrier. We will evaluate the formulations for their polydispersity, zeta potential and particle size; in addition, we will perform stability tests, irritative potential analysis, in vitro releasing profile, encapsulation efficiency, 2D and 3D cell culture experiments and in vivo retention. Considering the number of affected patients, this study can contribute to the scientific community as well as to society (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FUKUMORI, CLAUDIO; BRANCO, PAOLA CRISTINA; BARRETO, THAYNA; ISHIDA, KELLY; LOPES, LUCIANA B.. Development and cytotoxicity evaluation of multiple nanoemulsions for oral co-delivery of 5-fluorouracil and short chain triglycerides for colorectal cancer. European Journal of Pharmaceutical Sciences, v. 187, p. 15-pg., 2023-05-20. (18/13877-1, 14/50928-2, 19/03241-5)