Desenvolvimento e avaliação da atividade quimiopreventiva de nanopartículas contendo imiquimode em modelo murino de câncer de pele
Nenhuma Miniatura disponível
Data
2018-04-11
Autores
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Federal de Goiás
Resumo
Skin cancer has the highest incidence among all types of neoplasms and the
tendency is the increasing number of new cases in next decades, wich makes
necessary new modalities and treatment options. Chemotherapeutic agent
imiquimod is used in treatment of disease, but the high occurrence of local
and systemic adverse effects associated with its use as well as its low skin
permeation impair adherence and therapeutical effectiveness, respectively.
The aim of the present work was evaluate the antitumor activity of
nanocapsules imiquimod-loaded compared to its commercial product in
murine model of skin cancer. Polymeric nanocapsules containing imiquimod,
in the absence and presence of chitosan coating, were obtained by the
precipitation of preformed polymer technique and characterized by
encapsulation efficiency, size, zeta potential, pH, morphology (transmission
electron microscopy and scanning), optical scanning spectrophotometry and
in vitro release through dialysis membrane in pH 5.6 buffer. Presence of
chemical interactions between formulation components was evaluated by
thermogravimetric analysis and infrared spectroscopy. Detection of
crystalline structures was performed by X-ray diffractometry. The
nanocapsules and commercial imiquimod formulation antiagiogenic activity
was determined in a chicken embryo chorioallantoic membrane model.
Cutaneous permeation of nanocapsules imiquimod-loaded and commercial
imiquimod was determined in Swiss albino mice. The chemopreventive
activity of colloidal dispersions and the commercial imiquimod was evaluated
through the tumoral inhibition promoted by these treatments in a multi-
stage model of chemical carcinogenesis in Swiss mice. Encapsulation
efficiency, mean diameter, zeta potential and pH of uncoated nanocapsules
imiquimod-loaded were 92.5% ± 0.4; 249 ± 22.4 nm; -40.1 mV ± 3.7 and
5.4 ± 0.01 respectively, whereas for nanocapsules with cationic coating the
parameters found were: 88.6 ± 2.3%; 287.0 ± 12.6 nm; + 11.3 ± 0.5 mV
and 3.7 ± 0.0, respectively. The formulations morphology obtained by
scanning and transmission electron microscopy images confirmed the
presence of nanocapsules. In the stability analysis by optical scanning
spectrophotometry (Turbiscan), all dispersions obtained a backscattering
variation less than 2% over 5 weeks and were considered stable. In the in
vitro release assay, imiquimod-loaded nanoparticles obtained slower release
of the drug compared to free and commercial imiquimod. There were
chemical interactions between chitosan and other formulation components
evaluated by thermogravimetric and infrared studies. No crystalline structure
was detected by the X-ray diffraction technique for the coated and uncoated
imiquimod formulation. The dispersion of nanocapsules containing imiquimod
presented antiangiogenic activity superior than commercial formulation in
chicken embryo chorioallantoic membrane model. Nanocapsules containing
imiquimod both uncoated and coated with chitosan presented cutaneous
permeation in deep layers of the skin and inhibition in the chemically induced
carcinogenicity process superior than tumor control group and groups
treated with placebo nanoparticles while the commercial formulation
presented retention of the drug in superficial layers of the skin and did not
obtain a statistically significant reduction in the number of papillomas formed
compared to the carcinogenic control. These results allow to conclude,
therefore, that stable nanocarreadores were obtained and the
chemopreventive activity and the antiangiogenic effect of these systems
represent a promising alternative for the treatment of cutaneous neoplasias.
Descrição
Palavras-chave
Citação
DIAS, Marina França. Desenvolvimento e avaliação da atividade quimiopreventiva de nanopartículas contendo imiquimode em modelo murino de câncer de pele. 2018. 102 f. Tese (Doutorado em Nanotecnologia Farmacêutica em Rede) - Universidade Federal de Goiás, Goiânia, 2018.