Bougainvillea glabra Choisy bracts extract in free and liposomal forms reduce hyperplasia induced by let-60gain-of-function in Caenorhabditis elegans.

In this study, we evaluated the toxicological and antiproliferative effects of B. glabra Choisy bract extract (BGCE) in its free and loaded into liposomes forms administered to C. elegans mutants with let-60 gain-of-function (gf). Our results demonstrated that the concentration up to 75 µg CAE/mL of BGCE was safe for the worms. Notably, we developed BGCE-loaded liposomes to extend the pharmacological window up to 100 µg CAE/mL without toxicity. In addition, the extract and liposomes reduced the number and area of the multivulva formed in let-60 gf mutants. There was also an increase in the apoptotic signaling in the germline cells and increased longevity mediated through DAF-16 nuclear translocation with GST-4 activation in the treated animals. Our findings demonstrated that the BGCE-loaded liposomes possess antitumoral effects due to the activation of the apoptotic signaling and DAF-16 nuclear translocation.

Antiproliferative Cancer Cell and Fungicidal Effects of Yellow and Red Araçá (Psidium cattleianum Sabine) Fruit Extract.

Araçá is a native Brazil fruit, and has two morphological types, yellow and red; however, it is still little consumed by the population. Although there are few studies on the araçá fruit, some phytochemical propriety benefits have been described for this plant, such as antioxidant effects. To explore the benefits of araçá fruit, the physicochemical characteristics and in vitro toxicological effects of red and yellow araçá fruit were evaluated. In this work, the toxicity of araçá extracts in NIH/3T3 cell lines, the antiproliferative effects in cancer cell lines (C6, HT-29, and DU149), and the overall antifungal effects were evaluated. The irritant potential of araçá extracts was assessed by the HET-CAM test. The results demonstrated that the fruits are rich in fiber content and showed high phenols content. In addition, the araçá extracts had no present toxicity effects in cell lines; however, the red araçá extracts showed antiproliferative effects in HT-29 cancer cells at 50 mg/mL. The antifungal effects of araçá extract were promising in 23 isolates of Candida spp., and both araçá extracts showed no irritant effects. Therefore, this study demonstrated that red and yellow araçá fruit extract has promising biological and pharmacological effects that should be further explored.

The Importance of Skin Health Promotion for Children: Care with Makeup Use and Skin Cancer Prevention.

BACKGROUND: Numerous pathogenic complications affect the skin and are preventable, such as skin cancer, microbial diseases, dermal irritations, and anaphylaxis. In this context, the correct use of skin products, including sunscreens and child makeup, is important for promoting skin health and preventing adverse health conditions. OBJECTIVE: This study aimed to use educational and playful activities to promote skin health for students. METHODS: This project was development in a municipal elementary school (Rio Grande do Sul State, Brazil). The interventions were divided into three moments. In the first day, a questionnaire was applied to find out the students' previous knowledge about photoprotection. On the second day, an intervention lecture was held addressing issues related to photoprotection and the use of makeup. Finally, we played educational and ludic games and after, the questionnaire was reapplied. This was done to evaluate these actions' effectiveness regarding photoprotection and record their habits by applying a structured questionnaire at the beginning and end of the activities. RESULTS: Students received positively and interacted significantly during all activities performed. Regarding the impact of this study, we observed that ten times more students considered using sunscreen as something important at the end of the project, as only 8.16% of participants knew what skin cancer was at the beginning of the experiment. After the educational activities, this number rose to 72.37%, and 92.86% of girls reported wearing makeup, with more than half being expired or unlabeled and only 21.6% being appropriate for child use. CONCLUSION: The measures demonstrated effectively improve students' level of information regarding skin cancer prevention and indicated that inappropriate habits concerning makeup use in childhood are quite common, demonstrating the importance of educational interventions for children, since can improve your health.

In vivo and in vitro per se effect evaluation of Polycaprolactone and Eudragit® RS100-based nanoparticles.

Biodegradable polymeric nanocapsules (NC) present incredible characteristics as drug nanocarriers that optimize drug targeting. However, However, a more detailed isolated effect of polymer-based nanoparticles as drug carriers is required. This work aimed to evaluate the per se effect of blank-NC (NC-B) with different surface characteristics both in vitro and in vivo toxicity. NC1-B (Polysorbate 80 coated poly(ɛ-caprolactone) NC), NC2-B (polyethylene glycol 6000 coated poly(ɛ-caprolactone) NC), NC3-B (chitosan-coated poly(ɛ-caprolactone) NC) and NC4-B (Eudragit® RS100 NC) were prepared by nanoprecipitation method. Formulations were characterized by particle size, zeta potential, and pH. The in vitro cytotoxicity tests against tumor cell lines were performed (HepG2 and MCF-7). Antiviral activity was evaluated by MTT in Vero cells infected with HSV-1 (KOS strain). In vivo evaluation was performed in apomorphine-induced stereotypy in Wistar rats and locomotor activity distance, head movements, and rearing behavior were measured. NC1-B, NC2-B, NC3-B, and NC4-B had a diameter under 350 nm. The pH and zeta potential of formulations varied according to their coating. For in vitro evaluation of antitumor activity and antiviral activity, one-way ANOVA showed no significant differences in cell viability. In vivo tests showed low neurological effects. In conclusion, different surface characteristics of NC-B did not demonstrate toxicity against the evaluated cell lines HepG2 and MCF-7, antiviral effect against HSV-1, and the neurological effects in a stereotyping model were low and may be attributed to the per se effect of NC-B.

Judicialization of health: lawsuits for access to medicines in Uruguaiana-RS / Judicialização da saúde: ações de acesso a medicamentos em Uruguaiana-RS

INTRODUCTION: In Brazil, the right to health has a constitutional and universal provision. However, the judicial route has been widely used to access health goods and services. OBJECTIVE: To analyze the lawsuits of medicines filed by citizens of a Brazilian municipality. METHODS: Quantitative and retrospective study evaluating 652 lawsuits filed in 2016 conducted in Uruguaiana, state of Rio Grande do Sul. The information was made available by the State Department of Health. RESULTS: 55.5% of lawsuits filed were related to drugs provided by the public health system Sistema Único de Saúde (SUS). 44.5% did not fit into the guidelines of the Brazilian Policy for Pharmaceutical Services. Most of the lawsuits were filed by women over 60 years old. Regarding the therapeutic classification, the most requested drugs were for the nervous system. The most described pathological condition according to the ICD-10 (International Classification of Diseases) was Diabetes Mellitus. CONCLUSION: These data corroborate the situation found in other parts of the country, demonstrating the need to reorganize the Pharmaceutical Service Policy to ensure universal and equitable access to medicines, as described in the Federal Constitution.

INTRODUÇÃO: No Brasil, o direito à saúde tem previsão constitucional e universal. No entanto, a via judicial tem sido muito usada para acessar bens e serviços de saúde. OBJETIVO: Analisar as demandas judiciais de medicamentos movidas por cidadãos de um município brasileiro. MÉTODOS: Realizou-se um estudo quantitativo e retrospectivo que avaliou 652 ações judiciais no ano de 2016 em Uruguaiana, estado do Rio Grande do Sul. As informações foram disponibilizadas pela Secretaria de Saúde estadual. RESULTADOS: 55,5% das demandas estavam relacionados a medicamentos fornecidos pelo Sistema Único de Saúde (SUS). 44,5% não se enquadravam em nenhum dos componentes da Política Nacional de Assistência Farmacêutica do Brasil. A maioria dos processos foram movidos por mulheres acima de 60 anos. Em relação à classificação terapêutica, os medicamentos mais solicitados foram para o Sistema Nervoso. A condição patológica mais descrita, segundo o CID-10 (Classificação Internacional de Doenças) foi Diabetes Mellitus. CONCLUSÃO: Tais dados corroboram com a situação encontrada em outras partes do país, demonstrando a necessidade de reorganização da Assistência Farmacêutica para garantir o acesso universal e equitativo aos medicamentos, conforme descrito na Constituição Federal.

Evaluation of curcumin-loaded polymeric nanocapsules with different coatings in chick embryo model: influence on angiogenesis, teratogenesis and oxidative stress.

BACKGROUND: Curcumin (CUR) is a bioactive compound with several proven pharmacological properties. However, the major limitation for therapeutic use of CUR is its low bioavailability. In this sense, an alternative to this question is the use of polymeric nanocapsules (NC) as drug/nutraceutical delivery systems. Thus, the aim of current study was to assess the effect of CUR-loaded NC and their different coatings in chick embryo model, evaluating angiogenic, teratogenic and oxidative stress parameters. METHODS: The physicochemical characterization of unloaded and loaded NC with different coatings: (U-NC (P80), U-NC (PEG), U-NC (EUD), U-NC (CS), CUR-NC (P80), CUR-NC (PEG), CUR-NC (EUD) and CUR-NC (CS)) were performed. After 9 days of incubation, eggs were treated (10 mL/kg eggs; via injection) with NC (unloaded and loaded with CUR) and CUR-solution. In sequence, hen's egg test-chorioallantoic membrane (HET-CAM), angiogenic assay, external abnormalities, weight of embryos and oxidative stress markers (TBARS, NPSH, ROS and CAT) were analyzed. RESULTS: CUR-NC (P80, PEG, EUD and CS) treatments caused antiangiogenic and non-teratogenic effects in chick embryo model. Still, CUR-NC (P80), CUR-NC (PEG), CUR-NC (EUD) and CUR-NC (CS) did not alter markers of oxidative stress (TBARS, NPSH, CAT) studied. Only CUR-NC (EUD) caused increase in ROS levels. CONCLUSION: Wherefore, these findings of present study represent a advance in research of drug/nutraceutical delivery systems.

Leishmanicidal candidate LASSBio-1736, a cysteine protease inhibitor with favorable pharmacokinetics: low clearance and good distribution.

1. LASSBio-1736 ((E)-1-4(trifluoromethyl) benzylidene)-5-(2-4-dichlorozoyl) carbonylhydrazine) is proposed to be an oral cysteine protease leishmanicidal inhibitor. 2. This work aimed to investigate plasma pharmacokinetics, protein binding and tissue distribution of LASSBio-1736 in male Wistar rats. 3. LASSBio-1736 was administered to male Wistar rats at doses of 3.2 mg/kg intravenously and 12.6 mg/kg oral and intraperitoneal. The individual plasma-concentration profiles were determined by HPLC-UV and evaluated by non-compartmental and population pharmacokinetic analysis (Monolix 2016R1, Lixoft). Tissue distribution was evaluated after iv injection of 3.2 mg/kg drug by non-compartmental approach. 4. After intravenous administration, Vdss (1.79 L/kg), t ½ (23.1 h) and CLtot (56.1 mL/h/kg) were determined, and they were statistically similar (α =0.05) to oral and intraperitoneal pharmacokinetic parameters. The plasma profiles obtained after intravenous, oral and intraperitoneal administration of the compound were best fitted to a three-compartment and one-compartment open model with first-order absorption. 5. The intraperitoneal and oral bioavailability were around 40 and 15%, respectively. 6. Liver, spleen and skin tissues showed penetration of 340, 130 and 40%, respectively, with t ½ like plasma values. 7. LASSBio-1736 protein binding was 95 ± 2%. 8. The t ½, CLtot and tissue distribution of the compound agreed with the desired drug characteristics for leishmanicidal activity.

Optimization of Curcuma Oil/Quinine-Loaded Nanocapsules for Malaria Treatment.

Quinine, a treatment used in chloroquine-resistant falciparum malaria, was loaded into poly(ɛ-caprolactone) or Eudragit® RS100 nanocapsules using Curcuma oil as the oil-based core. Until now, the effect of cationic nanocapsules on malaria has not been reported. A 24 factorial design was adopted using, as independent variables, the concentration of Curcuma oil, presence of quinine, type of polymer, and aqueous surfactant. Diameter, zeta potential, and pH were the responses studied. The formulations were also evaluated for drug content, encapsulation efficiency, photostability, and antimalarial activity against Plasmodium berghei-infected mice. The type of polymer influenced all of the responses studied. Quinine-loaded Eudragit® RS100 (F13) and PCL nanocapsules (F9), both with polysorbate 80 coating, showed nanometric particle size, positive zeta potential, neutral pH, high drug content, and quinine photoprotection ability; thus, these nanocapsules were selected for in vivo tests. Both formulations showed lower levels of parasitemia from the beginning of the experiment (5.78 ± 3.60 and 4.76 ± 3.46% for F9 and F13, respectively) and highest survival mean time (15.3 ± 2.0 and 14.9 ± 5.6 days for F9 and F13, respectively). F9 and F13 showed significant survival curve compared to saline, thus demonstrating that nanoencapsulation improved bioefficacy of QN and co-encapsulated curcuminoids, regardless of the surface charge.

The use of Brazilian vegetable oils in nanoemulsions: an update on preparation and biological applications

ABSTRACT Vegetable oils present important pharmacological properties, which gained ground in the pharmaceutical field. Its encapsulation in nanoemulsions is considered a promising strategy to facilitate the applicability of these natural compounds and to potentiate the actions. These formulations offer several advantages for topical and systemic delivery of cosmetic and pharmaceutical agents including controlled droplet size, protection of the vegetable oil to photo, thermal and volatilization instability and ability to dissolve and stabilize lipophilic drugs. For these reasons, the aim of this review is to report on some characteristics, preparation methods, applications and especially analyze recent research available in the literature concerning the use of vegetable oils with therapeutic characteristics as lipid core in nanoemulsions, specially from Brazilian flora, such as babassu (Orbignya oleifera), aroeira (Schinus molle L.), andiroba (Carapa guaianiensis), casca-de-anta (Drimys brasiliensis Miers), sucupira (Pterodon emarginatus Vogel) and carqueja doce (Stenachaenium megapotamicum) oils.

Educational Activities for Rural and Urban Students to Prevent Skin Cancer in Rio Grande do Sul, Brazil.

BACKGROUND: Excessive exposure to the sun during childhood is strongly associated with the development of skin cancer in the future. The only way to prevent the development of skin cancer is to protect against ultraviolet radiation, which can be achieved through strategic awareness during childhood and adolescence. OBJECTIVE: The aim of this work was to evaluate the impact of educational activities for rural and urban students to promote the use of sunscreens and prevent skin cancer. MATERIALS AND METHODS: This study was carried out with students (9-12 years) of rural (n=70) and urban (n=70) schools in Rio Grande do Sul state, Brazil. The educational interventions were lectures and games. The impact of this strategy was evaluated through the application of a questionnaire before and after the interventions. RESULTS: Before the intervention, it was found around 50% of rural and urban students were not aware of the damage caused by sun exposure, often exposing themselves to UV radiation without use sunscreen ( ~ 25 %) and at the most critical times of the day/year. After the lectures we observed an improvement in the behavior of the students with regard to sun exposure and knowledge about skin cancer. CONCLUSIONS: The results of this study emphasize the importance of prevention strategies for skin cancer and promoting the use of sunscreens based educational strategies. The interventions were of great value in relation to disseminating knowledge on the subject.

Cutaneous melanoma: new advances in treatment.

Cutaneous melanoma is a challenge to treat. Over the last 30 years, no drug or combination of drugs demonstrated significant impact to improve patient survival. From 1995 to 2000, the use of cytokines such as interferon and interleukin become treatment options. In 2011, new drugs were approved by the U.S. Food and Drug Administration, including peginterferon alfa-2b for patients with stage III disease, vemurafenib for patients with metastatic melanoma with the BRAF V600E mutation, and ipilimumab, a monoclonal antibody directed to the CTLA-4 T lymphocyte receptor, to combat metastatic melanoma in patients who do not have the BRAF V600E mutation. Both ipilimumab and vemurafenib showed results in terms of overall survival. Other trials with inhibitors of other genes, such as the KIT gene and MEK, are underway in the search for new discoveries. The discovery of new treatments for advanced or metastatic disease aims to relieve symptoms and improve patient quality of life.

Cutaneous melanoma: new advances in treatment

Cutaneous melanoma is a challenge to treat. Over the last 30 years, no drug or combination of drugs demonstrated significant impact to improve patient survival. From 1995 to 2000, the use of cytokines such as interferon and interleukin become treatment options. In 2011, new drugs were approved by the U.S. Food and Drug Administration, including peginterferon alfa-2b for patients with stage III disease, vemurafenib for patients with metastatic melanoma with the BRAF V600E mutation, and ipilimumab, a monoclonal antibody directed to the CTLA-4 T lymphocyte receptor, to combat metastatic melanoma in patients who do not have the BRAF V600E mutation. Both ipilimumab and vemurafenib showed results in terms of overall survival. Other trials with inhibitors of other genes, such as the KIT gene and MEK, are underway in the search for new discoveries. The discovery of new treatments for advanced or metastatic disease aims to relieve symptoms and improve patient quality of life.

Development of innovative oil-core self-organized nanovesicles prepared with chitosan and lecithin using a 2(3) full-factorial design.

The aim of this study was to develop innovative nanosystems with isopropyl myristate as the oil core of self-assembly nanovesicles constituted of chitosan and lecithin using a 2(3) factorial design. The factors analyzed were chitosan (X1, levels 4 and 8 mg/ml), oil (X2, levels 10 and 20 mg/ml) and lecithin (X3, levels 4 and 8 mg/ml). The responses evaluated were diameter, zeta potential, pH, viscosity, and backscattering analysis. The bioavailability was evaluated after oral administration of clozapine free and nanoencapsulated in rats. The diameter ranged from 0.348 to 1.5 µm for F2 (X1, 4; X2, 10; X3, 8 mg/ml) and F7 (X1, 8; X2, 20; X3, 4 mg/ml), respectively. Laser diffractometry analysis revealed only one diameter population for all batches. Zeta potential was positive, being influenced by X1 and X2/X3 association. Viscosity values were dependent on the X1 and X2 concentrations used. A structure proposed for the nanosystem consists of chitosan forming the hydrophilic shell layer that protects the core comprised of lecithin and the hydrophobic groups of oil. The AUC0-∞ was almost 3 times higher with the clozapine nanoencapsuted in relation to free drug. It was developed a new nanosystem which is able of improving the absorption of drugs.

Influência da adição de extrato de chá-verde sobre a estabilidade e efeito fotoprotetor de emulsões fps 15 / Influence of green tea extract on the stability and photoprotective effect of spf 15 emulsions

A inserção de produtos de origem vegetal em cosméticos podem melhorar as suas características. Nesse estudo, objetivou-se o desenvolvimento de formulações fotoprotetoras contendo extrato glicólico de Camelia sinensis, a avaliação da atividade fotoprotetora in vitro após a adição do extrato vegetal, bem como a avaliação das características organolépticas, a determinação do valor de pH e comportamento reológico durante 30 dias de avaliação, quando as formulações foram armazenadas nas temperaturas de 25±2°C; 5±2 °C e 40±2 °C. Após 15 dias, alterações nas características organolépticas e reológicas foram observadas nas formulações armazenadas em altas temperaturas. Em 30 dias, as formulações mantidas a temperatura ambiente e em geladeira mantiveram as características organolépticas, apesar das alterações reológicas. Observou-se uma tendência a aumento do efeito fotoprotetor com a formulação contendo FPS15 e extrato glicólico de chá verde, entretanto, não se pode atribuir melhora na estabilidade física da emulsão pela adição do extrato.

The addition of plant material to a cosmetic may improve its characteristics. The stability profile allows the performance, safety, efficacy and consumer acceptance of an emulsion to be assessed. A stability study provides information about the behavior of the product over a given time interval, under various environmental conditions. The aims of this study were to prepare sunscreen formulations containing a glycolic extract of green tea (Camellia sinensis) and to assess the photoprotective activity in vitro, the organoleptic characteristics, pH and rheological behavior over a period of 30 days, during which the formulations were stored at temperatures of 25±2°C, 5±2°C and 40±2°C. After 15 days, changes in rheological characteristics were observed in the formulation stored at the higher temperatures. After 30 days, changes were observed at other temperatures. The addition of the extract significantly changed the rheological profile of the sunscreen formulations tested. An increase in the photoprotective effect was observed when the emulsion base was compared with the emulsion containing green tea extract. However, there was no evidence of an improvement of stability when the plant extract was added to the emulsions.