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Development of functionalized nanoparticles with folate for the delivery of glycoalkaloids of Solanum lycocarpum and biological evaluation using 2D and 3D cell culture models

Grant number: 15/14665-0
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2015
Effective date (End): November 02, 2018
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Maria Vitória Lopes Badra Bentley
Grantee:Mariza Abreu Miranda
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):17/09025-7 - Investigating the mechanism of action of Solanum lycocarpum glycoalkaloids free and encapsulated in nanoparticles: in vitro study and 3D cells platforms of bladder cancer and other cancer cells lines, BE.EP.PD


The bladder cancer (BC) is the second most common malignancy of the urinary tract and is accounted for about 165,000 deaths/year in the worldwide. The main therapies for BC include BCG immunotherapy and chemotherapy. However, the effectiveness of these therapies is limited. The BC intravesical treatment is a challenge due to low permeability of the molecules into urothelium and low residence time of the drug at the site due to periodic emptying of the bladder. Thus, a strategy to overcome these challenges is utilizing the application of nanothecnology. The glycoalkaloids (GA) solasonine (SS) and solamargine (SM), extracted from the fruits of Solanum lycocarpum, have showed anticarcinogenic properties. Based on this, the current project aims at the development and characterization polymeric nanoparticles functionalized containing alkaloidic extract of the S. lycocarpum fruits, with high concentration of SS and SM. The major goal is to design a targeted system that will increase the residence time of these active molecules in bladder and its permeation in the urothelium. For this, the system containing the extract, rich in GA, will be encapsulated and subsequently, the particles will be functionalized in order to obtain a site-specific system, which will be characterized by several techniques. After the optimization of nanoparticles, the formulation will be tested in vitro assays using 2D and 3D bladder cancer cell models, and in molecular assays. From these studies, it is expected to develop nanoparticles formulation system for the treatment of BC with compounds derived from the secondary metabolism of the S. lycocarpum and, additionally, a platform of cytotoxicity studies will be developed using 2D and 3D cell culture 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)
MIRANDA, MARIZA A.; MARCATO, PRISCYLA D.; CARVALHO, IVANA P. S.; SILVA, LETICIA B.; RIBEIRO, DIEGO L.; AMARAL, ROBSON; SWIECH, KAMILLA; BASTOS, JAIRO K.; PASCHOAL, JONAS A. R.; DOS REIS, RODOLFO B.; et al. Assessing the cytotoxic potential of glycoalkaloidic extract in nanoparticles against bladder cancer cells. Journal of Pharmacy and Pharmacology, v. 71, n. 10, . (14/50928-2, 15/14665-0)

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Filed patent(s) as a result of this research project

FORMULAÇÃO DE NANOPARTÍCULAS POLIMÉRICAS E SEU USO BR1020170212629 - Universidade de São Paulo (USP) . Priscyla Daniely Marcato Gaspari; Ivana Pereira Santos Carvalho; Jairo Kenupp Bastos; Letícia Bueno da Silva; Maria Vitória Lopes Badra Bentley; Mariza Abreu Miranda - October 2017, 03