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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

Grant number: 20/06093-4
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): December 01, 2021
Effective date (End): November 30, 2024
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Marlus Chorilli
Grantee:Aline Martins dos Santos
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated scholarship(s):23/15694-0 - Topochemical engineering in design of retrograded starch/pectin microparticles as potential carriers for colon-specific drug delivery, BE.EP.PD

Abstract

There remain several key challenges to existing for Colorectal Cancer (CRC) therapy by intravenous route, mainly associated to the targeted delivery of drugs in the colon and/or tumor region as well as the systemic side effects reduction. 5-fluorouracil (5-FU) is one of the first-line chemotherapeutic drugs in the CRC therapy; however, it has short plasma half-life, unstable absorption in the Gastrointestinal Tract (GIT), variation in its pharmacokinetics and problems related to its high hydrophilia. Liposomes are among the most effective delivery systems used in cancer therapy due to its unique properties, such as small diameter, high stability, the ability to incorporate of hydrophilic and hydrophobic drugs and structural similarity to the cell membrane, demonstrating highly compatibility with biological tissue. Although it has therapeutic efficacy, liposomes can be destabilized in GIT, preventing its use by the oral route. Hence, it is important to engineer oral systems that allow to achieve the delivery of liposome/drugs in the colonic region, protecting them against premature degradation or release on the upper GIT. In this context, this research project aims to carry liposomes in colon-specific microparticles based on retrograded starch and pectin as a promising strategy for targeting 5-FU to the colonic region via oral delivery, promoting a local treatment of CRC with reduction of side effects. In order to prove the effectiveness against CRC therapy, the characterization of systems and validation of the methodologies will be performed, as well as in vitro biological assays using HCT-116 cell lines and in vivo from animal models. (AU)

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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)
DOS SANTOS, ALINE MARTINS; TAVARES JUNIOR, ALBERTO GOMES; CARVALHO, SUZANA GONCALVES; CHORILLI, MARLUS. An Updated Review on Properties, Nanodelivery Systems, and Analytical Methods for the Determination of 5-Fluorouracil in Pharmaceutical and Biological Samples. CURRENT PHARMACEUTICAL DESIGN, v. 28, n. 18, p. 12-pg., . (20/06093-4, 14/50928-2)
DE PAULA, MARIANA CARLOMAGNO; CARVALHO, SUZANA GONCALVES; SILVESTRE, AMANDA LETICIA POLLI; DOS SANTOS, ALINE MARTINS; MENEGUIN, ANDREIA BAGLIOTTI; CHORILLI, MARLUS. The role of hyaluronic acid in the design and functionalization of nanoparticles for the treatment of colorectal cancer. Carbohydrate Polymers, v. 320, p. 19-pg., . (20/06093-4, 14/50928-2)

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