Sistemas nanoestruturados multicompartimentais para coencapsulação e liberação controlada de paclitaxel e genisteína: desenvolvimento, caracterização e avaliação da atividade antitumoral in vivo

• Autor(a) principal: Mendes, Lívia Palmerston
• Data de Publicação: 2012
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/00130000024n8
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/4349
• topic: Paclitaxel; Genisteína; Nanopartículas; Angiogênese; Liberação controlada; Co-encapsulação; Atividade antitumoral in vivo; Paclitaxel; Genistein; Nanoparticles; Angiogenesis; Controlled release; Co-encapsulation; In vivo antitumor activity; FARMACIA::ANALISE E CONTROLE E MEDICAMENTOS

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.