Sistemas nanoestruturados multicompartimentais para coencapsulação e liberação controlada de paclitaxel e genisteína: desenvolvimento, caracterização e avaliação da atividade antitumoral in vivo
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2012-09-20
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Universidade Federal de Goiás
Resumo
Nanostructured polymeric and lipid systems are capable of improving therapeutic
index of encapsulated drugs, especially when it comes to antitumor drugs. In this
work, co-encapsulation of paclitaxel (PTX) and genistein (GEN) was obtained by
developing a multilayered nanocarrier for controlled release of drugs.
Nanocapsules (NC) encapsulating PTX were obtained by interfacial deposition of
preformed polymer method. They were further coated with a phospholipid bilayer
entrapping GEN and their physical-chemical properties were characterized.
Coated nanoparticles presented an entrapment efficiency of about 98% for both
drugs. Particles were in the range of 150 nm and showed a monomodal
distribution. Multiple light scattering analyses presented an increase of only 2% of
the backscattering profile both in the top and in the bottom of the sample,
indicating a slight sedimentation and creaming behaviors, both reversible
phenomena. In vitro drug release showed that GEN was completely released
within 48 hours, whereas in that same period, less than 10% of PTX was released
and reached almost 70% after 60 days of analysis. The results suggest that we
have developed a biodegradable device for a sustained release of GEN and PTX
in different stages. In vivo antitumor activity assays with Ehrlich ascites tumor
(EAT) bearing mice evaluated intra-tumoral administration of the developed
formulation in three different concentrations of PTX in the presence or absence of
GEN. Results presented more than 90% tumor inhibition in EAT-bearing mice
compared to the control group when a dose of nanostructured PTX about 5 times
lower than the equivalent dose used in conventional chemotherapy was used.
When a low dose of PTX (0.2 mg/kg/day) was used in the treatment, 11% tumor
inhibition was achieved, but when associated with a dose of 12 mg/kg/day of GEN,
there was 44% tumor inhibition and a decrease of about 58% in VEGF levels
compared to animals treated with blank nanoparticles. The antiangiogenic effect of
GEN was evident when associated with PTX, inhibiting formation of new vascular
network formed by tortuous and congested vessels in peritoneal region of mice
when compared with groups treated only with PTX. Co-encapsulation of GEN and
PTX in a controlled-release multicompartimental nanosystem promoted additive
effect of antiangiogenic activity associated with antitumor effect, intending to be a
formulation with high potential for anticancer treatment.
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MENDES, L. P. Sistemas nanoestruturados multicompartimentais para coencapsulação e liberação controlada de paclitaxel e genisteína: desenvolvimento, caracterização e avaliação da atividade antitumoral in vivo. 2012. 60 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2012.