Development and characterization of methotrexate-loadedfunctionalized PLA nanoparticles for potential cancer therapy
Nanoparticles, functionalization, methotrexate, emulsification with solvent evaporation, fluorescent.
Methotrexate (MTX) is an antimetabolite drug used in the chemotherapy of
cancer, autoimmune diseases and uveits. Its pharmacokinetic limitations
include short half-life time and difficulty to across biological barriers. Cationic
nanoparticles (NP) can improve the drug efficacy due to the ability of overcome
biological barriers reaching specific tissues. This study focused on the
preparation and optimization of cationic and fluorescent functionalized MTXloaded
polylactide (PLA) NP by the emulsification with solvent evaporation. The
effect of different surfactants (polysorbate 80, sorbitan monooleate 80, polyvinyl
alcohol (PVA), Poloxamer 188 and Poloxamer 407), as well as distinct
surfactant/polymer ratios were tested. The particle size, zeta potential, Atomic
Force Microscopy (AFM) images and encapsulation efficiency were used as
performance parameters to select the best formulation.The selected formulation
was functionalized with polyethyleneimine (PEI 25 kDa) in PEI:PLA proportion
of 1:5 and fluorescent labeled with fluorescein isothiocyanate (FITC). MTXloaded
nanoparticles exhibited size of 260.53 nm ± 1.80, zeta potential of
+34.13 mV ± 2.13,withencapsulation efficiency of 83.89% ± 3.56.AFM images
demonstrated spherical and smooth particles, which have the fluorescence
assessed by fluorescence microscopy images, Fourier transforms Infrared
(FTIR)-ATR and flow cytometry. Thus, cationic and fluorescent functionalized
MTX-loaded PLA nanoparticles were successfully optimized by using
emulsification with solvent evaporation.