RESUMO:O uso de plantas medicinais tem sido muito significativo nos últimos anos, sendo incentivado pela Organização Mundial de Saúde (OMS). Synadenium umbellatum Pax, Euphorbiacea (vulgo cola-nota, cancerola, milagrosa) tem o látex usado empiricamente como antitumoral e antiinflamatório. Por existir espécies tóxicas nesta família e visando à segurança no uso de extratos vegetais, tal estudo avaliou a toxicidade pré-clínica do látex e do extrato etanólico das folhas (EEF) de S. umbellatum, por via oral, em ratas Wistar. O estudo seguiu diretrizes do Guideline 423 (toxicidade aguda) e Guideline 407 (toxicidade subaguda) da OECD (Organisation for Economic Cooperation and Development). Na toxicidade aguda do látex e do EEF, não se observou letalidade nem alterações fisiológicas e comportamentais das ratas na dose de 2000 mg/ kg, sendo praticamente atóxico. Porém, na análise histopatológica, o látex ocasionou congestão e infiltrado leucocitário nos rins, fígado e pulmões, efeitos não observados com o EEF. Na toxicidade subaguda, doses de 50, 100 e 200 mg/kg de EEF não produziram alterações dose-dependentes significativas nos parâmetros laboratoriais e fisiológicos, nem alterações macroscópicas e histopatológicas nos órgãos das ratas. Contudo, o uso crônico da planta S. umbellatum merece mais estudos.Unitermos: Synadenium umbellatum, toxicidade aguda, toxicidade subaguda, toxicidade pré-clinica.ABSTRACT: "Acute and subacute toxicity studies of the latex and of the ethanolic extract of the leaves of Synadenium umbellatum Pax in rats". The use of medicinal plants has been being very significant in the last years, being the use encouraged by WHO. Synadenium umbellatum Pax, Euphorbiacea (popularly known as cola-note, cancerola, miraculous) has the latex used empirically as anti-cancerous and anti-inflammatory. For there being toxic species in this family and aiming at the safety in the use of vegetable extracts, such study evaluated the pre-clinical toxicity of the latex and of the ethanolic extract of the leaves (EEL) of S. umbellatum, administrated by oral route, in Wistar female rats. The study followed OECD's Guidelines for test of acute toxicity (Guideline 423) and for subacute toxicity (Guideline 407). In the acute toxicity of latex and EEL, behavioral and physiological alterations were not observed neither animal's death in the dose level of 2,000 mg/kg. However, the latex caused congestion and leukocytes infiltration of the kidneys, liver and lungs, effects not observed with EEL. In the subacute toxicity, dose levels of 50, 100 and 200 mg/kg of EEL did not produced significant dose-dependent alterations in the lab results and no physiologic, macroscopic and hystopathological alterations. EEL of S. umbellatum is practically poisonless in acute exposure; already the latex can cause hystological damages. The chronic use of S. umbellatum needs more specific studies.

Nanostructured drug delivery systems are based on biocompatible and biodegradable components. Composition, size and membrane surface properties are characteristics that may influence cell viability in cytotoxicity assays. In this work, four nanostructured systems commonly used for drug delivery were prepared and cytotoxicity was evaluated on human lymphocytes and Balb/c 3T3 fibroblasts. The hemolytic potential was also investigated. Polymeric nanocapsules (NC) and nanospheres (NS), nanostructured lipid carriers (NLC) and liposomes were prepared and characterized for size, distribution, zeta potential and number per volume of the colloidal dispersion. Cell viability was evaluated, 24 and 48h, by MTT and neutral red assays (NR). Cells were incubated with each particle in eight different dilutions varying from 2.1×10(4) to 2.1×10(11)particles/mL. Diameter of nanoparticles was between 130 and 200nm, all samples exhibited narrow size distribution (polydispersity index below 0.1) and zeta potential varied from -6.8 to -19.5mV. NC, NS and NLC reduced cell viability in a dilution dependent manner. For these nanoparticles, the higher number of particles induced cell death for both cell types. Liposomes did not cause loss of cell viability even at the highest number of particles. Results suggest that, depending on the kind of nanoparticle, the number of particles in the dispersion can negatively influence cell viability in pre-clinical drug development.

RESUMO:Punica granatum L., Punicaceae, amplamente usada no Brasil, foi avaliada quanto ao seu potencial antitumoral in vitro e in vivo. Investigou-se in vitro a citotoxicidade do extrato etanólico do fruto e folha da P. granatum utilizando células K-562 e células do Tumor Ascítico de Ehrlich (TAE), pelos métodos de redução do MTT e exclusão do azul de tripano. Nos estudos in vivo avaliou-se o aumento da sobrevida de animais portadores do TAE e tratados, por via oral, com diferentes doses dos extratos etanólicos da P. granatum (12,5; 25; 50 e 100 mg/kg) por dez dias consecutivos. Além disso, nestes animais analisou-se o potencial de inibição tumoral e a atividade antiangiogênica da P. granatum. Os resultados dos estudos in vitro demonstraram uma redução na viabilidade das células K-562 e do TAE, concentração-dependente, nos métodos investigados. Os resultados in vivo demonstraram aumento da sobrevida dos animais portadores do TAE tratados, de forma dose-dependente. Em paralelo, observou-se diminuição do número de células tumorais na cavidade peritoneal dos animais portadores e tratados. Além disto, os tratamentos empregados reduziram o padrão de vascularização da parede abdominal. Dessa forma, os dados apresentados revelaram que o extrato de P. granatum possui atividade antitumoral in vitro e in vivo em paralelo a redução da angiogênese peritoneal.Unitermos: Punica granatum, Punicaceae, atividade antitumoral, citotoxicidade, angiogênese, tumor ascítico de Ehrlich.ABSTRACT: "Cytotoxic and antiangiogenic activities of Punica granatum L., Punicaceae". Punica granatum L., a plant widely used in Brazil, was tested for its antitumor and antiangiogenic activities in vitro and in vivo. In this work, the in vitro cytotoxicity was evaluated using the K-562 cell line and Ehrlich ascites tumour cells, by MTT tetrazolium reduction test and the trypan blue exclusion test. In vivo studies investigated the increase in the survival time of Ehrlich tumour-bearing mice after treatment with different doses of Punica granatum L. ethanol extract (12.5; 25; 50 e and 100 mg/kg), by gavages, for ten consecutive days. In addition, we also investigated the tumour inhibition potential and antiangiogenic activity of this plant. In vitro results demonstrated a decrease of K-562 and Ehrlich ascites tumour cells viability, with both methods used, in a dependent-manner concentration. In vivo results showed a significant antitumor activity against Ehrlich ascites tumour growth, increasing survival time. In parallel, we detected a significant inhibition of the tumour growth, along with a decrease in the vascular pattern of the peritoneal wall. Thus, the data presented herein clearly showed that Punica granatum L. has antitumor and antiangiogenic activities.

The present study confirmed the ethnopharmacological use of Palicourea coriacea as a diuretic agent in the experimental condition tested here. Additionally, this work supports the importance of the preservation of local knowledge as well as the conservation of Brazilian biodiversity.

Itraconazole (ITZ) has a broad spectrum of action and is commonly used for the treatment of fungal infections. Topic administration of ITZ is a promising strategy to improve vulvovaginal candidiasis treatment, which can be further optimized by its encapsulation in nanoparticles to increase drug delivery and reduce ITZ toxicity. In this work, we designed polycaprolactone nanoparticles containing ITZ and evaluated in vivo the efficacy of this yet unexplored approach. Nanocapsules (ITZ-NC) and nanospheres (ITZ-NS) were obtained by nanoprecipitation. ITZ-NC presented encapsulation efficiency of 99%, mean diameter of 190 nm, PDI 0.1 and zeta potential of -15 mV. ITZ-NS showed encapsulation efficiency of 97%, mean diameter of 120 nm, PDI 0.1 and zeta potential of -10 mV. Both particles were efficiently freeze-dried using 10% trehalose + 10% sucrose. Nanoparticles were then incorporated in a viscous formulation for vaginal application in female Balb/C mice infected with Candida albicans. Fungal load was significantly reduced in infected animals after treatment with ITZ-NC but not with ITZ-NS, compared to animals treated with ITZ solution. Histological analysis showed a clear difference between vaginal tissues of ITZ-NC and ITZ-NS and ITZ solution-treated animals, which correlated with IL-1β and TNF-α quantification. Animals treated with ITZ-NC showed reduced cytokine levels and healthy tissue characteristics, while animals treated with ITZ-NS and ITZ solution showed increased IL-1β and TNF-α levels and typical tissue inflammation. Our results demonstrate the potential of ITZ-NC to improve the treatment of vulvovaginal candidiasis after topical application in the vagina, opening new perspectives for the treatment of this disease.