Liberação controlada por magnetohipertermia de doxorrubicina em magnetolipossomas direcionados ao receptor de superfície celular folato

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2018-10-08

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Universidade Federal de Goiás

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Doxorubicin is one of the most commonly used antineoplastic agents in the treatment of solid tumors, such as soft tissue tumors and osteosarcomas. However, the high occurrence of cardiotoxic side effects due to its prolonged use causes damages to adherence and therapeutic efficacy. In order to diminish the side effects, during the present research magnetoliposomes with magnetic nanoparticles coencapsulating doxorubicin were developed in their aqueous interior vectors for the folate receptor aiming controlled release by magnetohypertermia. This work was divided in four stages: optimization and validation of analytical methodology to quantify doxorubicin; synthesis of magnetic fluids with different layers of coverage; development of magnetoliposomes coencapsulating doxorubicin with and without vectorization in order to compare if the effectiveness of the vectorization and in vitro studies for the chemotherapy effectiveness of the liposomal formulation against the B16F10 cell was verified. The magnetoliposomes were prepared by the lipid film hydration method followed by extrusion and the physical-chemical and morphological results showed that the liposomal formulations have an average size close to 150 nm. The magnetic particles have an average size of 13 nm, high saturation magnetization, superparamagnetic behavior and are composed by manganese ferrite with different layers of coverings. The magnetoliposomes were able to generate heat through magnetohyperthermia with alternating magnetic field. The liposomal formulation of magnetoliposome with vectorized doxorubicin to the folate receptor showed higher antitumor activity when compared to formulation without vectorization. When compared to hyperthermia test, it showed that the increase in temperature is linked to a better effect with the drug for a greater cytotoxic effect. These results suggest, therefore, that the obtaining of a liposomal formulation towards the antitumor activity represents a promising alternative associated to the codelivery chemotherapeutic and magnetic nanoparticles directed at the tumor tissue.

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CINTRA, E. R. Liberação controlada por magnetohipertermia de doxorrubicina em magnetolipossomas direcionados ao receptor de superfície celular folato. 2018. 120 f. Tese (Doutorado em Nanotecnologia Farmacêutica em Rede) - Universidade Federal de Goiás, Goiânia, 2018.