An Updated Review on Properties, Nanodelivery Systems, and Analytical Methods for the Determination of 5-Fluorouracil in Pharmaceutical and Biological Samples

Author(s)

dos Santos, Aline Martins ; Tavares Junior, Alberto Gomes ; Carvalho, Suzana Goncalves ; Chorilli, Marlus

• Document type: Journal article
• Source: CURRENT PHARMACEUTICAL DESIGN; v. 28, n. 18, p. 12-pg., 2022-01-01.

Abstract

5-Fluorouracil (5-FU) is an antimetabolite drug used for over 70 years as first-line chemotherapy to treat various types of cancer, such as head, neck, breast, and colorectal cancer. 5-FU acts mainly by inhibiting thymidylate synthase, thereby interfering with deoxyribonucleic acid (DNA) replication or by 5-FU incorporating into DNA, causing damage to the sequence of nucleotides. Being analogous to uracil, 5-FU enters cells using the same transport mechanism, where a is converted into active metabolites such as fluorouridine triphosphate (FUTP), fluorodeoxyuridine monophosphate (FdUMP), and fluorodeoxyuridine triphosphate (FdUTP). Currently, there are several nano delivery systems being developed and evaluated at the preclinical level to overcome existing limitations to 5-FU chemotherapy, including liposomes, polymeric nanoparticles, polymeric micelles, nanoemulsions, mesoporous silica nanoparticles, and solid lipid nanoparticles. Therefore, it is essential to choose and develop suitable analytical methods for the quantification of 5-FU and its metabolites (5-fluorouridine and 5-fluoro-2-deoxyuridine) in pharmaceutical and biological samples. Among the analytical techniques, chromatographic methods are commonly the most used for the quantification of 5-FU from different matrices. However, other analytical methods have also been developed for the determination of 5-FU, such as electrochemical methods, a sensitive, selective, and precise technique, in addition to having a reduced cost. Here, we first review the physicochemical properties, mechanism of action, and advances in 5-FU nanodelivery systems. Next, we summarize the current progress of other chromatographic methods described to determine 5-FU. Lastly, we discuss the advantages of electrochemical methods for the identification and quantification of 5-FU and its metabolites in pharmaceutical and biological samples. (AU)

• FAPESP's process: 20/06093-4 - Multifunctional systems based on liposomes carried into retrograded starch and pectin microparticles for colon-specific release of 5-fluorouracil in the treatment of Colorectal Cancer
• Grantee: Aline Martins dos Santos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants