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SILVA, L. B. Preparation, characterization and cytotoxic potential evaluated in bladder cancer cells of nanostructured lipid carriers functionalized with folate encapsulated quercetin. 2016. 105f. Dissertation (Master). Faculdade de Ciências Farmacêuticas de Ribeirão Preto – Universidade de São Paulo, Ribeirão Preto, 2016. Bladder cancer (BC) is the second most prevalent tumor of urinary tract. Currently the main BC therapies have low effectiveness, high recurrence rate and several adverse effects. Thus, new molecule have been investigate to CB therapy. Quercetin (QT) is a flavonoid with interesting properties for cancer therapy such as inhibition of cancer cell proliferation and apoptosis. However, QT is an unstable and photosensitive compound. Therefore, QT encapsulated in nanostructure lipid carriers (NLC) functionalized with folate (F-NLC) might be an alternative targeting system of QT for tumor cell and can be strategy to overcome intravesical CB therapy challenges. The QT encapsulation can improve QT stability, increase its permeation in the urothelium and uptake in tumor cells, increase retention time in the bladder and enhancing its pharmacological efficacy. Aims of this study were preparation, characterization of NLC-QT and F-NLC-QT and cytotoxic evaluation of these particles in BC cells. NLC and F-NLC were prepared by ultrasonication method. NLC were funcionalized by conjugated between surfactant Pluronic and folate (PL68F). This conjugation was characterized by proton nuclear magnetic resonance spectroscopy (NMR). The particles were characterized regarding to size, polydispersity index (PdI), zeta potential (ZP), crystallinity, encapsulation efficiency (EE) and morphology. Furthermore, stability, release profile, cytotoxicity and antioxidant activity of QT encapsulated or not in NLC, were evaluated. RMN spectrums confirmed the PF68 functionalization, exhibiting peaks attributed to PF68 and folate. Size, PdI and ZP of NCL were respectively 176.5 nm, 0.124 and -11.4, whereas F-NLC showed 197.9 nm of size, 0.160 of PdI and ZP of -17.5mV. The QT encapsulation did not affect these physical parameters. Low values of crystalization index (~28) might promote high EE of quercetin (~98%). NLC shows spherical shape, sustained release profile of QT and were stable for 330 days. IC50 of NLC-QT (87.4 μg/mL) was smaller thanthe IC50 of F-NLC-QT (94.9 μg/mL). This difference might be explained by the increase of NLC uptake by endocytosis mediated by folate receptor. NLC-QT and F-NLC-QT showed high antioxidant activity. Therefore, our results suggest that QT-F-NLC is a carry system with potential for future BC therapy that show size smaller than 200 nm, low PdI, high long-term stability, high EE and antioxidant activity, sustained release and cytotoxic to CB cells (RT4).

Preparação, caracterização e avaliação do potencial citotóxico in vitro de carreadores lipídicos nanoestruturados funcionalizados com folato encapsulando quercetina em células de câncer de bexiga