Obtenção de nanopartículas magnéticas sensíveis a estímulos para aplicações biomédicas

Abstract

Polymeric particles with magnetic properties can be useful for in vivo therapeutic applications, as agents for controlled drug release, for ex vivo applications, as agents for the extraction of cancer cells, and finally, for the diagnosis in vitro. The search for biocompatible and smart materials as agents for the encapsulation of magnetic particles, leads to the use of stmuli-responsive polymers. In therapeutic applications, this technology is based on the localization and the concentration of the particles containing the drug in the area of interest by applying a magnetic field. This step is followed by the release of the drug, using the sensitive properties of the polymers. In this context, this thesis is devoted to the preparation of nanoparticles constituted by a stimuli-responsive polymer matrix and particles of iron oxide (γ-Fe2O3 e Fe3O4). First of all, we performed the synthesis of poly(NVCL-co-AA)-based nanogels using the precipitation polymerization method. Poly(N-vinilcaprolactama) (PNVCL) is a thermo-responsive polymer which presents the lower critical solution temperature (LCST) near the physiological temperature (35-38 °C) and it is well known by its greater biocompatibility, in comparison with other themallysensitive polymers. On the other hand, the poly(acrylic acid) (PAA) is known by its sensibility to changes in the enviromental pH. In this stage, the influence of some synthesis parameters on the particles diameter, polydispersity and themally-sensitive behavior of the nanogels was evaluated. The pH-sensibility behavior was also studied as a function of the AA concentration in the synthesis. As a second step, the study of the incorporation of dextran-coated magnetic nanoparticles in the PNVCL-based nanogels using the inverse miniemulsion polymerization was preformed. The thermo-responsive magnetic nanogels were characterized in terms of particles diameter (PD) and particles size distribution (PSD) using light scattering. The temperature sensitivity of the magnetic nanogels was also studied by light scattering, with measurements of particles diameter as a function of temperature. The magnetization measurements were obtained on a vibrating sample magnetometer (VSM). Analysis of infra-red (FTIR) and X-ray diffraction revealed qualitatively the incorporation of magnetic nanoparticles. The incorporation efficiency of iron oxide nanoparticles was studied by thermo-gravimetric analysis (TGA) and magnetic measurements. The morphological characteristics of the magnetic nanogels were observed by transmission electron microscopy (TEM).