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

Grant number: 19/03241-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2020
Effective date (End): December 31, 2022
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Luciana Biagini Lopes
Grantee:Claudio Fukumori
Home 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)

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