masterThesis
Micropartículas contendo nanopartículas de quitosana usando sulfato e genipina para liberação modificada da triancinolona: obtenção, caracterização e estudo em células tumorais
Fecha
2015-03-31Registro en:
FONSÊCA, Gabriela Diniz. Micropartículas contendo nanopartículas de quitosana usando sulfato e genipina para liberação modificada da triancinolona: obtenção, caracterização e estudo em células tumorais. 2015. 80f. Dissertação (Mestrado em Ciências Farmacêuticas) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2015.
Autor
Fonsêca, Gabriela Diniz
Resumen
Chitosan is a polymer biocompatibility and biodegradability widely used in drug delivery
systems. The co-crosslinking of chitosan with sodium sulfate and genipin, to form particulate
systems is related of making them more resistant to acidic pH and to modulate the release
kinetics for the oral route. Triamcinolone is a glucocorticoid with anti-inflammatory and
immunosuppressive actions. The nanoparticles were prepared by co-crosslinking and
characterized for particle size, PDI, zeta potential, crosslinking degree, encapsulation rate,
morphology, infrared spectroscopy, thermal analysis, release kinetics and cells studies. The
nanoparticles were prepared initially without genipin with sodium sulphate and the particles
parameters were monitored in function of different ratio of drug / polymer, different
concentrations of sodium sulfate and polysorbate 80 and the drip mode of crosslinkers on
polymers. After optimizing conditions, the chosen system parameters
without genipin included mean diameter of 312.20 ± 5.70 nm, PDI 0.342 ± 0.013 and zeta
potential of 20.18 ± 2.28 mV. The genipin was introduced into the system analyzing different
concentrations (0.5, 1.0 and 2.0 mM) and crosslinking times (3, 6, 12 and
24 h). Evaluating crosslinking time with genipin (0.5 mM) it was showed that varying
the genipin reaction time the systems size ranged from 235.1 to 334.4 nm, the PDI from 0.321
to 0.392 and zeta potential 20.92 to 30.39 mV. The crosslinking degree that coud vary
from 14 to 30 %. Nanoparticles without genipina, 6 h and 24 h crosslinking time were dried
by spray-drying method. Analysis by scanning electron micrograph (SEM) revealed that the
microparticles showed spherical morphology. The encapsulation rate was 75 ± 2.3 % using
validated HPLC methodology. The infrared analysis showed chemical interactions between
the components of the formulation. Thermal analysis showed that systems with a higher
degree of crosslinking had a higher thermal stability. On release kinetics, increasing the
degree of crosslinking was able to decrease the concentration and rate of release of
triamcinolone. In studies with liver cancer cells (HepG2) and colon (HT-29),
the microparticulate prepared with triamcinolone and 24 h of crosslinking
with genipin showed a potential for antitumor activity in hepatic cell line HepG2. Therefore, a
new delivery system for triamcinolone on polymeric nanoparticles of chitosan cocrosslinked
with genipin and sodium sulfate was obtained with hepatic antitumor potential.