Multifunctionalized systems-based chitosan nanoparticles anchored with methotrexat...
| Grant number: | 17/25846-0 |
| Support type: | Scholarships abroad - Research Internship - Doctorate |
| Effective date (Start): | April 01, 2018 |
| Effective date (End): | September 30, 2018 |
| Field of knowledge: | Health Sciences - Pharmacy - Pharmaceutical Technology |
| Principal Investigator: | Maria Palmira Daflon Gremião |
| Grantee: | Aline Martins dos Santos |
| Supervisor abroad: | Kristofer Thurecht |
| Home Institution: | Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil |
| Local de pesquisa : | University of Queensland, Brisbane (UQ), Australia |
| Associated to the scholarship: | 16/01464-9 - Multifunctionalized systems-based chitosan nanoparticles anchored with methotrexate and incorporated into resistant starch/pectin microparticles for colon-specific release of 5-fluourouracil, BP.DR |
Abstract Colorectal cancer (CRC) is the third highest worldwide incidence and the fourth leading cause of cancer-related mortality, highlighting the need of new therapeutic alternatives for the treatment of this pathology. The pharmaceutical nanotechnology is an important technological tool for the development of new drug delivery systems for the treatment of CRC. The nanoparticles enable the encapsulation of low-stability drugs, protecting them against premature degradation, the modulation of the drug release rates and/or the targeting of drug for specific organs or tissues. 5-fluorouracil (5-FU) is one of the most widely used drugs in the treatment of the CRC, however, the rapid catabolism (about 80%) by dihydropyrimidine dehydrogenase enzyme and non-selective action against epithelium of gastrointestinal tract (GIT), limit their therapeutic efficacy. Meanwhile, its efficacy in therapy CRC can be enhanced by combination with methotrexate (MTX). MTX is an antifolate cytotoxic drug, extensively used in the treatment of several solid tumors including CRC. Due to structural similarity with folic acid, MTX can be actively internalized by the cancerous cells through the binding of MTX to folate receptor. Therefore, the coupling of MTX on the nanoparticle'structure represents a rational strategy for targeted therapy, allowing the target of chemotherapeutics to the cancer cells and improvement of the nanoparticle tumor biointerface interaction. Furthermore, the encapsulation of nanoparticles in colon-specific delivery systems that avoid premature degradation or uptake of the nanoparticles during the passage through the upper GIT is a promising approach to achieving the targeted delivery of chemotherapeutics to the colon from an oral administration. In this context, in this PhD's project developed by Aline Martins dos Santos student, chitosan (CS) nanoparticles, and microparticles of resistant starch (RS) and pectin (P) has been explored, since these polymers have the desirable properties of mucoadhesiviness and biodegradability dependent on colonic enzymes. This project aims the evaluation of the potential for colon-targeted delivery of 5-FU-loaded CS nanoparticles, functionalized with MTX and incorporated in RS/P microparticles, using a model of in vivo biodistribution by small animal optical imaging, to be held at the Australian Institute of Bioengineering and Nanotechnology, University of Queensland, in Australia, under the supervision of Prof. Dr. Kristofer J. Thurecht. This study will contribute decisively to the understanding of the in vivo release of nanoparticles from microparticles following oral administration, and their distribution and retention in the colorectal region. | |