NANOPARTÍCULAS DE POLI (ÁCIDO LÁTICO) FUNCIONALIZADAS PARA
POTENCIAL USO NO TRATAMENTO DE CÂNCER
Cationic Nanoparticles. Methotrexate. Emulsification-solvent evaporation. Fluorescent.
Cancer is the second worldwide cause of death, surpassed only by
cardiovascular diseases. The traditional cancer therapy has limitations because
of the undesirable side effects associated with the drugs, and because of their
non-specificity for neoplastic tissue. Methotrexate (MTX) is an antimetábolite
used in some types of cancer and autoimmune diseases, which has limitations
related to rapid plasma elimination, and its non-specific distribution. Polymeric
nanoparticles have been widely studied as alternatives for improving drug
efficacy, overcoming the limitations of biological barriers, as well as for targeting
specific tissues. The aim of the present work was the preparation and
optimization of cationic and fluorescent poly (lactic acid) (PLA) nanoparticles through the emulsificationd with solvent evaporation method. In order to obtain
stable and small size nanoparticles, the effect of the type and concentration of
different surfactants, as well as the different concentrations of polymer were
evaluated through the dynamic light scattering technique, which allowed to
evaluate the diameter, Zeta potential and polydispersity of the nanoparticles.
After the optimization of the parameters, nanoparticles in the order of 260 nm
were obtained and functionalized with polyethyleneimine (PEI), turning the
surface of the particle into cationic. PLA binding was further performed with the fluorescein isothiocyanate fluorescent dye (FITC). The FITC-labeled PLA was
used to produce fluorescent nanoparticles, which were analyzed by flow cytometry, showing intense fluorescence. After the the obtainment of
fluorescent and positively charged nanoparticles, the drug load was performed
with MTX, the entrapment efficiency was 83.89% ± 3.56. Preliminary studies in
kidney tumoral cells (786-0) and non-tumor kidney (HEK 293T) demonstrated
that MTX-loaded nanoparticles were able to increase the antiproliferative
activity compared to the pure MTX. Thus, cationic and fluorescent
functionalized MTX-loaded PLA nanoparticles were successfully optimized by
using emulsification with solvent evaporation.