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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-Doctorate
Effective date (Start): December 01, 2021
Effective date (End): November 30, 2023
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


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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