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Evaluation of the potential of transferrin-functionalized liposomes for docetaxel delivery in the treatment of prostate cancer

Grant number: 17/25190-8
Support type:Scholarships in Brazil - Master
Effective date (Start): April 01, 2018
Effective date (End): November 16, 2019
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Marlus Chorilli
Grantee:Mariza Aires Fernandes
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated scholarship(s):18/26422-2 - Evaluation of the potential of transferrin-functionalized liposomes for docetaxel delivery for the treatment of prostate cancer, BE.EP.MS

Abstract

Prostate cancer is the most common urological malignancy and the second leading cause of cancer mortality in the world. Treatment is initiated through surgical interventions covering radical prostatectomy, followed by active surveillance, radiotherapy, as well as therapies involving androgen deprivation and immunotherapies. Chemotherapy is also widely used and recent studies have demonstrated remarkable control of prostate cancer growth using docetaxel (DTX), which works by inhibiting cell proliferation from sustained mitotic block during cell cycle metaphase / anaphase, which promotes polymerization of stable microtubules and prevents cell division. However, DTX has side effects associated with both drug and formulation toxicity, Taxotere®. As a consequence, the development of nanotechnology drug delivery systems, such as liposomes, has been promising for the treatment of prostate cancer, because of the multiple favorable characteristics of these nanosystems, such as biocompatibility and biodegradability. One attractive approach is the surface modification of liposomes with specific ligands of the regulated receptors on the surfaces of tumor cells, such as transferrin receptors, which are overexpressed in prostate tumor cells. The present work aims to: develop, characterize and evaluate the in vitro cytotoxicity of transferrin-functionalized liposomes for the delivery of docetaxel in the treatment of prostate cancer. The liposomes will be obtained by means of the classic lipid film hydration technique. The lipid composition will include phosphatidylcholine and cholesterol in mole ratios to be defined. For the functionalized liposome the lipid DSPE-PEG (2000) maleimide (MAL) will be included in the molar ratio to be defined, to allow the thioether reaction between the thiolated protein and the maleimide group. The liposomes will be characterized by transmission electron microscopy (TEM), particle size measurements, PDI and zeta potential and circular dichroism (CD). The release assays will be performed for free and associated liposomes, then the samples will be filtered and analyzed by the HPLC method. Finally, in vitro biological assays will be performed to evaluate the cytotoxicity of the formulation. Therefore, it is expected to obtain an innovative formulation that allows the direct delivery of docetaxel in order to obtain efficient therapy for prostate 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)
AIRES-FERNANDES, MARIZA; ELOY, JOSIMAR O.; VICTORELLI, FRANCESCA DAMIANI; FERREIRA, PAULA SCANAVEZ; PIRONI, ANDRESSA MARIA; CHORILLI, MARLUS. Reversed-phase high-performance liquid chromatography: A fast and efficient analytical method to quantify docetaxel-loaded pegylated liposomes in release study. JOURNAL OF SEPARATION SCIENCE, v. 44, n. 21 SEP 2021. Web of Science Citations: 0.
FERNANDES, MARIZA AIRES; ELOY, JOSIMAR O.; LUIZ, MARCELA TAVARES; RAMOS JUNIOR, SERGIO LUIZ; BORGES, JULIO CESAR; DE LA FUENTE, LAURA RODRIGUEZ; LUIS, CLARA ORTEGA-DE SAN; MARCHETTI, JULIANA MALDONADO; SANTOS-MARTINEZ, MARIA J.; CHORILLI, MARLUS. Transferrin-functionalized liposomes for docetaxel delivery to prostate cancer cells. COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, v. 611, FEB 20 2021. Web of Science Citations: 0.

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