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Multifunctionalized systems-based chitosan nanoparticles anchored with methotrexate and incorporated into resistant starch/pectin microparticles for colon-specific release of 5-fluourouracil

Grant number: 16/01464-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2017
Effective date (End): July 31, 2019
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Maria Palmira Daflon Gremião
Grantee:Aline Martins dos Santos
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated scholarship(s):17/25846-0 - Evaluation of the potential for colon-specific delivery of 5-fluorouracil nanoparticles and 5-fluorouracil nanoparticles incorporated in resistant starch/pectin microparticles, using a model of in vivo biodistribution by small animal optical imaging, BE.EP.DR

Abstract

The treatment of the colorectal cancer is conducted by administering high doses of antineoplasic agents due to its lack of specificity, leading to severe side effects. Among these drugs, 5-fluorouracil is one of the more effective and although suffers first pass metabolism its efficacy may be enhanced by combination with methotrexate, which due to structural similarity with folic acid, promotes internalization by the cancerous cells. The improvement of the residence time of the drug in the tumor tissue can be achieved using nanoparticles, which due its small size favor the system penetration through the tumor vessels and mucus layer. The use of chitosan for the development of nanoparticles should be highlighted due their important mucoadhesive properties. The nanoparticles can be incorporated into microparticles based on natural polysaccharides with biodegradability dependent on colonic enzymes, as resistant starch and pectin, in order to reach its colon specific release and to promote the local action of 5- fluorouracil, minimizing side effects. In this sense, the development of chitosan nanoparticles functionalized with methotrexate and incorporated in resistant starch/pectin microparticles for oral administration is a potential strategy for colonic release of 5-fluorouracil, leading to increased anti-tumor activity and optimization of the treatment of colorectal cancer. (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; MENEGUIN, ANDREIA BAGLIOTTI; FONSECA-SANTOS, BRUNO; CHAVES DE SOUZA, MAURICIO PALMEIRA; BARBOZA FERREIRA, LEONARDO MIZIARA; SABIO, RAFAEL MIGUEL; CHORILLI, MARLUS; DAFLON GREMIAO, MARIA PALMIRA. The role of stabilizers and mechanical processes on physico-chemical and anti-inflammatory properties of methotrexate nanosuspensions. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 57, JUN 2020. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.