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Previous issue date: 2015-03-31 === Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) === Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) === A quitosana ? um co-pol?mero biocompat?vel e biodegrad?vel amplamente usado em sistemas
de libera??o de f?rmacos. A co-reticula??o da quitosana com sulfato de s?dio e genipina para
forma??o de sistemas particulados ? capaz de tornar estes mais resistentes ao pH ?cido e
modificar a cin?tica de libera??o de f?rmacos para a via oral. A triancinolona ?
um glicocortic?ide de ampla aplica??o terap?utica por suas a??es antiinflamat?ria e
imunossupressora. Os sistemas particulados foram preparados por co-reticula??o e
caracterizadas quanto ao tamanho de part?cula, PDI, potencial zeta, grau de reticula??o, taxa
de encapsula??o, MEV, espectroscopia de infravermelho, an?lise t?rmica, cin?tica de
libera??o e estudo em c?lulas tumorais. Inicialmente foram preparadas nanopart?culas com
sulfato de s?dio, sem genipina, contendo triancinolona, avaliando a propor??o do volume das
fases f?rmaco/pol?mero, concentra??o de sulfato de s?dio e polissorbato 80, tempo e modo de
imers?o das fases. O sistema definido para a reticula??o com a genipina apresentou tamanho
de 312,20 ? 5,70 nm, PDI 0,342 ? 0,013 e potencial zeta 20,18 ? 2,28 mV. A genipina foi
introduzida no sistema em diferentes concentra??es (0,5; 1,0 e 2,0 mM) e tempos de
reticula??o (3, 6, 12 e 24 h). Na an?lise do tempo de reticula??o com genipina 0,5 mM, os
sistemas obtiveram tamanho de 235,1 a 334,4 nm, PDI de 0,321 a 0,392 e potencial zeta de
20,92 a 30,39 mV, com grau de reticula??o que variou de 14 a
30 %. As nanopart?culas sem genipina, 6 h e 24 h de reticula??o foram escolhidas para a
secagem por spray-drying, formando micropart?culas de nanopart?culas. A an?lise por
micrografia eletr?nica de varredura revelou que as micropart?culas apresentaram morfologia
esf?rica. A taxa de encapsula??o foi de 75 ? 2,3% usando metodologia CLAE validada. A
caracteriza??o dos sistemas por infravermelho evidenciou as intera??es entre os componentes
da formula??o. A an?lise t?rmica mostrou que os sistemas com maior grau de reticula??o,
apresentaram uma maior estabilidade t?rmica. Na cin?tica de libera??o, o aumento do grau
de reticula??o foi capaz de diminuir a velocidade de libera??o da triancinolona. Nos
estudos com c?lulas HepG2 e HT-29 os sistemas microparticulados contendo triancinolona e
genipina com tempo de reticula??o de 24 h apresentaram um potencial para atividade
antitumoral nas c?lulas de linhagem hep?ticas HepG2. Com isso, um novo sistema de
libera??o a base de quitosana obtido por co-reticula??o com sulfato de s?dio
e genipina contendo triancinolona foi obtido com potencial antitumoral hep?tico. === 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.
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