Síntese e caracterização de microesferas ferromagnéticas para utilização em hipertermia

Abstract

Several different sorts of clinical procedures have been developed to cancer therapy during the last century. The classical cancer treatment includes the total excision of tumor and adjacent tissues in combination with chemotherapy, immunotherapy or radiation treatment. The development of hyperthermia has brought an additional driving force to cancer therapy. In the hyperthermia treatment magnetic particles introduced in the tumors are inductively heated by a magnetic field at moderate temperatures (41- 43 °C). The temperatures that exceed 41 °C inactivate the cancer cells preserving the normal cells of the surround tissues. Due to their biocompatible properties, poly (2-hydroxy methylmethacrylate) (PHEMA) microspheres and nanospheres are among the most promising carriers for the magnetic particles. An important part of our laboratory’s research is focused on the encapsulation of the Y3Fe5-xA1xO12 (YFeAl) magnetic particles by using biocompatible polymers for hyperthermia treatment. When the microencapsulated magnetic materials are protected from extracellular enzymatic degradation and the citotoxicity of the YFeAl due to metal presence may be avoided. Poly (2-hydroxy methylmethacrylate) microspheres containing the polycrystalline particles of Y3Fe5-xAlxO12 (0≤x≤2) were prepared by suspension polymerization in a batch reactor using ammonium persulfate and as initiator and the cross-linker ethylene glycydil dimethacrylate EGDMA. The synthetized microspheres were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The Curie temperature (Tc) was determined from magnetic susceptibility measurements in the temperature rang of 223-573 K. The derivative curve for the size of distribution determined by differential granulometric analysis and the SEM micrograph for PHEMA/YFeAl microspheres showed good monodispersities (> 80%). The XRD analysis reveals that yttrium aluminum iron garnet samples appear as a single phase. SEM micrograph of YIG reveals the presence of aggregates of irregular fine particles. The Curie temperatures (Tc) of YIG estimated from the magnetization curves decreased with the aluminum content probably due to the reduction of the number of the main magnetic interaction. The Tc values for the PHEMA microspheres containing YFeAl in the composition range of 1.5≤x≤1.8 were near to room temperature, indicating that the synthetized microspheres are promissory materials for the hyperthermia treatment. In order 16 to evaluate the possible influence of the PHEMA/YFeAl microspheres on cells, cytotoxicity assay was carried out. It was observed that the presence of the microspheres did not affect the cell viability or the culture growth rate. According to the results obtained in this work, the synthetized PHEMA/YFeAl microspheres seems to be promising material for the hyperthermia treatment. The PHEMA/YFeAl microspheres modulates the release of the 5- Fluorouracil (5-FU) from magnetic microspheres, avoiding the high concentrations of the drug that may cause severe systemic toxicity. Loaded PHEMA/YFeAl microspheres showed a non-significant hyperemia, displaying low inflammatory reaction after implantation. The results obtained in this work are promising according to the design of the drug delivery systems in which is necessary to control both, the total amount of the drug and the kinetic profile.