Title:	Nanopartículas de PLGA contendo clorambucil e funcionalizadas com O-estearoil manose : síntese, caracterização e avaliação da ação citotóxica em células tumorais MCF-7
Other Titles:	Chlorambucil-containing PLGA nanoparticles functionalized with Ostearoyl mannose : synthesis, characterization and evaluation of cytotoxic action in MCF-7 tumor cells
Authors:	Costa, Antônio Oliveira da
Orientador(es)::	Gomes, Anderson de Jesus
Assunto::	Fármacos nanoestruturados Câncer - tratamento Mamas - câncer - tratamento Clorambucil (CLB)
Issue Date:	10-Jun-2020
Data de defesa::	8-Nov-2019
Citation:	COSTA, Antônio Oliveira da. Nanopartículas de PLGA contendo clorambucil e funcionalizadas com O-estearoil manose: síntese, caracterização e avaliação da ação citotóxica em células tumorais MCF-72019. 106 f., il. Tese (Doutorado em Nanociência e Nanobiotecnologia)—Universidade de Brasília, Brasília, 2019.
Abstract:	Chlorambucil (CLB) is a drug that has been used to treat a variety of cancers, such as chronic lymphoid leukemia, Hodgkin's and non-Hodgkin's lymphoma, choriocarcinoma, ovarian carcinoma, and breast carcinoma. However, it still has limited use due to its adverse effects. One promising approach to minimizing these effects is their targeted delivery through nanostructured drug delivery systems such as PLGA polymer nanoparticles. Another promising approach for minimizing adverse drug effects is the surface functionalization of the nanoparticulate system with specific ligands aimed at targeted delivery of the drug to the specific target. Thus, the objective of this work was to formulate and characterize PLGA nanoparticles containing the chlorambucil drug and functionalized with O-stearoyl mannose, as well as to evaluate their cytotoxicity in MCF-7 and non-tumor NIH-3T3 tumor cells. For this, O-stearoyl mannose (OEM) was synthesized from stearoyl chloride and D-mannose which was later used in the formulation of nanoparticles (NPs). The nanoparticles were obtained by the simple emulsification and solvent evaporation method, characterized by dynamic light scattering, electrophoretic scattering, scanning electron microscopy, UV-VIS spectroscopy, fluorescence spectroscopy, FTIR spectroscopy, TGA and DSC thermal analysis, drug encapsulation efficiency and drug release profile from nanoparticles. The drug release kinetics was also evaluated by four mathematical models and nanoparticle cytotoxicity was evaluated in MCF-7 and NIH-3T3 cells. As a result, the nanoparticles had an average hydrodynamic diameter size ranging from 185.5 to 220.7 nm, zeta potential from -14.2 to -17.7 mV, PdI from 0.186 to 0.288, had encapsulation efficiency greater than 61%. Scanning electron microscopy showed that the NPs showed spherical morphology, with the NPs containing OEM in the formulation having a hough appearance. UV-VIS, fluorescence and FTIR spectroscopic analyzes confirmed the incorporation and integrity of CLB in the NPs, as well as the functionalization of the NPs with the OEM. The results of thermal analysis showed that the NPs remain thermally stable without mass loss up to 200 °C and that the polymer matrix has a glass transition temperature above 43 °C. In vitro release studies showed a biphasic and sustained release profile for both systems, functionalized and non- functionalized NPs, which were analyzed considering first-order, Korsmeyer-Peppas mathematical models, Fick diffusion and the combination of the first order and Fick diffusion, where the release of CLB from the NPs obtained the best fit with the combination of first order and Fick diffusion mathematical models. Results of MCF-7 and NIH-3T3 cell viability assays indicated that the functionalization of the NPs with the OEM can promote their greater internalization, and that the NP-CLB-OEM at the concentration of 64 μg/mL were higher efficient in reducing cell viability of MCF-7 cells compared to other NPs at the same concentration. Thus, the formulated NPs present themselves as a promising sustained release drug release system, which may contribute to the increase of selectivity and therapeutic efficiency indices and reduction of adverse effects.
metadata.dc.description.unidade:	Instituto de Ciências Biológicas (IB)
Description:	Tese (Doutorado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Nanociência e Nanobiotecnologia, 2019.
metadata.dc.description.ppg:	Programa de Pós-Graduação em Nanociência e Nanobiotecnologia
Agência financiadora:	Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
Appears in Collections:	Teses, dissertações e produtos pós-doutorado

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