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Development of solid lipid nanocarriers functionalized with folate encapsulating quercetin for bladder cancer therapy

Grant number: 13/24308-4
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): September 01, 2014
Effective date (End): August 31, 2016
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Priscyla Daniely Marcato Gaspari
Grantee:Letícia Bueno Silva
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Urinary bladder cancer (BC) is the second most common malignancy of the urinary tract and in Brazil there are about 3167 deaths/year due to this type of cancer. Currently the main UBC therapies include immunotherapy with BCG and chemotherapy. But the effectiveness of these therapies is low, have a high recurrence rate and various adverse effects. Thus, new therapeutic strategies have been studied such as the use of compounds from the secondary metabolism of plants as quercetin. Quercetin is a flavanoid, which has antioxidant and anticarcinogenic properties acting on different molecular mechanisms that are interesting for cancer therapy. However, application of these molecules in the treatment of BC by intravesical route is a challenge because the molecules have low permeability in the urothelium, low residence time in the bladder, due to the periodic emptying and filling of the bladder, and, in general, multiple administrations are required causing high incidence of infection and local pain. Thus, a strategy to overcome these challenges is the nanomedicine, more specifically sustained release systems. A sustained drug release and a system to target to tumor cells can be obtained with these systems. Thereby, these systems can increase the therapy effectiveness and decrease the side effects. In this line, the aim of this project is development and characterization of nanostructured lipid carrier functionalized with folate as carrying system of quercetin in order to achieving a specific-target system to tumor cells. The functionalized particles will be prepared by emulsion and sonication method. The diameter and zeta potential will be characterized by photon correlation spectroscopy, morphology by atomic force microscopy and crystallinity by differencial scanning calorimetry. Moreover, the encapsulation efficiency and release profile of quercetin will be evaluated. The effectiveness of the developed nanostructured systems will be evaluated by the antioxidant activity of free and encapsulated quercetin, in vitro cytotoxicity of free and encapsulated quercetin on bladder cancer cells. In addition, the uptake of nanoparticles in bladder cancer cells will be analysed by confocal laser scanning microscopy images. (AU)

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVA, Letícia Bueno. Preparation, characterization and cytotoxic potential evaluated in bladder cancer cells of nanostructured lipid carriers functionalized with folate encapsulated quercetin. 2016. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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