Microesferas contendo extrato padronizado de Cecropia glaziovi Snethl para o tratamento da hipertensão arterial

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Programa de Pós-Graduação em FarmáciaCecropia glaziovi Snethl, distribuída no sul e no sudeste do Brasil, vem sendo amplamente utilizada pela população principalmente por sua atividade cardiovascular. Recentemente, o extrato desta planta, desenvolvido por nosso grupo de pesquisa, apresentou capacidade vasodilatadora in vitro satisfatória. O presente trabalho mostra a otimização deste extrato em relação ao conteúdo de ácido clorogênico (ACG) e ácido cafeico (ACF), associados a esta atividade, e a sua incorporação em sistema microestruturado, visando a obtenção de um medicamento de liberação controlada de administração oral para o tratamento da hipertensão arterial. O extrato seco otimizado (ESO) por análise de metodologia de superfície de resposta, apresentou condições ótimas de extração concomitante de ACG e ACF com 18 % de droga, etanol (27 %, V/V) durante 3 dias de maceração. O efeito do ESO no teste de reatividade em aorta de ratos mostrou ser semelhante à ação do controle positivo acetilcolina, considerado um resultado excelente por tratar-se de um extrato bruto sem nenhuma purificação. O extrato padronizado foi encapsulado em micropartículas pela técnica de dupla emulsão a/o/a, usando como matriz polimérica o ácido poli (lático-co-glicólico) (PLGA). Um planejamento experimental avaliando os efeitos da quantidade de polímero, quantidade de extrato, volume da fase de extração e tipo de polímero resultou na formação de partículas com tamanhos entre 91 a 220 µm com distribuição normal e valores de eficiência de encapsulação (EE) abaixo de 14 %. Em um segundo planejamento experimental, o balanço da pressão osmótica pela adição de concentrações crescentes de NaCl na fase aquosa externa da dupla emulsão influenciou significativamente as características das micropartículas permitindo um aumento na EE porém com modificação no comportamento de liberação das micropartículas.Cecropia glaziovi Snethl, widely distributed in southern and south-eastern Brazil, has been extensively used in Brazilian folk medicine mainly due to its cardiovascular activities. Recently, the extract of this plant, developed by our research group, showed satisfactory vasodilation capacity in vitro. This study shows the standardization of the crude extract maximizing ACG and ACF extraction associated with its biological activity evaluation and its encapsulation in a microparticulate system in order to obtain an oral drug delivery system for the treatment of hypertension. The Response Surface Methodology allowed the determination of an optimized set of extraction conditions with 18 % of drug, ethanol (27 %, V/V) during 3 days of maceration in order to produce the standardized dry extract (SDE). The effect of this extract in the vasorelaxant activity on rat aorta rings pre-contracted with phenylephrine showed to be similar to the acetylcholine (control), which is considered an excellent result for a crude extract without purification. Thereafter, the extract was used in the preparation and characterization of microparticles using the technique of double emulsion W/O/W using acid poly(lactic-co-glycolic) (PLGA) as polymer matrix. An experimental design evaluating the factors amount of polymer, amount of extract, volume of extraction phase and polymer type showed particle formation with size ranging from 91 to 220 ìm, narrow size distribution and efficiency encapsulation (EE) values below 14 %. In a second experimental design the osmotic pressure balance by the addition of increasing concentrations of NaCl in the external aqueous phase significantly influenced all microparticle characteristics allowing increase in the EE but with changes in the release behaviour of the microparticles

Desenvolvimento e caracterização de sistema fitoterápico nanoestruturado de Cecropia glaziovii Snethl para o tratamento do herpes labial

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2016.Estudos utilizando folhas de Cecropia glaziovii Snethl evidenciaram grande potencial anti-herpético relacionado, principalmente, aos compostos fenólicos presentes nesta espécie. Sendo assim, o objetivo do trabalho foi aliar o potencial terapêutico desta planta associado a novas estratégicas tecnológicas, tal qual desenvolvimento de nanopartículas (NPs) a serem empregadas na elaboração de um medicamento fitoterápico. Neste trabalho, o preparo de fração enriquecida em flavonoides (FEF-Cg) a partir desta planta foi padronizado. A avaliação da atividade antiviral contra o vírus HSV-1 da FEF-Cg evidenciou um índice de seletividade > 106,33. NPs de PLGA contendo a FEF-Cg, preparadas por dupla emulsão seguida da evaporação do solvente, apresentaram diâmetro médio de 205,2 ± 1,2 nm, PDI 0,15 ± 5,44, potencial zeta de -35,59 ± 5,33 mV e valores de EE de 64,65 ± 3,09%, com um teor de 0,65 ± 3,14% em fração. Um estudo de estabilidade, realizado em temperatura ambiente (25oC) por 60 dias, demonstrou maior estabilidade para o sistema contendo os surfactantes monooleato de sorbitano e poloxamer 188 nas fases orgânica e aquosa, respectivamente. Estudos do perfil de liberação e da degradação do polímero demonstraram uma liberação controlada da FEF-Cg através da matriz polimérica e uma redução significante na massa molar do polímero durante 21 dias. Estas NPs não exibiram citotoxicidade em células Vero nas concentrações testadas e apresentaram um potencial efeito anti-herpético contra o vírus HSV-1. Filmes e hidrogéis termossensíveis de quitosana foram preparados com quatro concentrações de NPs de PLGA (1, 3, 5 e 10%, m/m) e caracterizados quanto a sua morfologia, propriedades químicas e mecânicas e citotoxicidade. Diferentes concentrações de NaHCO3 foram utilizadas na preparação de hidrogel de quitosana visando obter um hidrogel termossensível homogêneo. A caracterização das formulações mostrou que todos os hidrogéis exibiram propriedades termossensíveis alterando de um comportamento líquido à 25oC para um comportamento de gel à 37oC. Em resumo, os filmes e hidrogéis nanocompósitos demonstraram ser promissores como sistemas de liberação no tratamento de infecções por herpes.Abstract : Studies employing Cecropia glaziovii Snethl leaves have shown great potential regarding its antiherpes activity, mainly related to the phenolic compounds present in this species. Thus, the main goal of this work was to combine the therapeutic potential of this species to new technological strategies targeting at the development of an herbal nanoparticulate system (NPs) to be used in the preparation of a phytotherapeutic formulation. In this work the preparation procedures for the EFF-Cg were standardized. The antiviral activity was tested against HSV-1, the results for selectivity index values was > 106.33. PLGA NPs containing the EFF-Cg were prepared using the double-emulsion evaporation method and it presented a mean diameter of 205.2 ± 1.2 nm, PDI of 0.15 ± 5.44, zeta potential of -35.59 ± 5.33 mV, EE value of 64.65 ± 3.09% and EFF-Cg load of 0.65 ± 3.14%. A stability study of the formulations performed in room temperature (25oC) for 60 days, demonstrated highest colloidal stability using the sorbitan monooleate and the poloxamer 188 surfactant in the organic and aqueous phases, respectively. Drug delivery study and polymer degradation demonstrated a controlled release of the drug through the polymer matrix and a significant reduction of molecular weight of the polymer at 21-day period. These NPs not exhibit cytotoxicity over Vero cells and presented a potential antiherpes effect against HSV-1 virus. The chitosan films and chitosan thermosensitive hydrogels were prepared with four different concentrations of PLGA NPs (1, 3, 5 and 10%, w/w) and were characterized in term of morphology, chemical, mechanical properties and cytotoxicity. Chitosan thermosensitive hydrogel was prepared with different NaHCO3 concentrations to choice the optimal condition to obtain homogeneous thermosensitive hydrogel. The formulations were characterized and the results showed that all hydrogels exhibited thermosensitive property, changing from liquid-like behavior at 25°C to gel-like behavior at 37°C. In summary, films and hydrogels nanocomposites demonstrated a promising system for the effective drug delivery in the treatment of herpes infections

ATLANTIC EPIPHYTES: a data set of vascular and non-vascular epiphyte plants and lichens from the Atlantic Forest

Epiphytes are hyper-diverse and one of the frequently undervalued life forms in plant surveys and biodiversity inventories. Epiphytes of the Atlantic Forest, one of the most endangered ecosystems in the world, have high endemism and radiated recently in the Pliocene. We aimed to (1) compile an extensive Atlantic Forest data set on vascular, non-vascular plants (including hemiepiphytes), and lichen epiphyte species occurrence and abundance; (2) describe the epiphyte distribution in the Atlantic Forest, in order to indicate future sampling efforts. Our work presents the first epiphyte data set with information on abundance and occurrence of epiphyte phorophyte species. All data compiled here come from three main sources provided by the authors: published sources (comprising peer-reviewed articles, books, and theses), unpublished data, and herbarium data. We compiled a data set composed of 2,095 species, from 89,270 holo/hemiepiphyte records, in the Atlantic Forest of Brazil, Argentina, Paraguay, and Uruguay, recorded from 1824 to early 2018. Most of the records were from qualitative data (occurrence only, 88%), well distributed throughout the Atlantic Forest. For quantitative records, the most common sampling method was individual trees (71%), followed by plot sampling (19%), and transect sampling (10%). Angiosperms (81%) were the most frequently registered group, and Bromeliaceae and Orchidaceae were the families with the greatest number of records (27,272 and 21,945, respectively). Ferns and Lycophytes presented fewer records than Angiosperms, and Polypodiaceae were the most recorded family, and more concentrated in the Southern and Southeastern regions. Data on non-vascular plants and lichens were scarce, with a few disjunct records concentrated in the Northeastern region of the Atlantic Forest. For all non-vascular plant records, Lejeuneaceae, a family of liverworts, was the most recorded family. We hope that our effort to organize scattered epiphyte data help advance the knowledge of epiphyte ecology, as well as our understanding of macroecological and biogeographical patterns in the Atlantic Forest. No copyright restrictions are associated with the data set. Please cite this Ecology Data Paper if the data are used in publication and teaching events. © 2019 The Authors. Ecology © 2019 The Ecological Society of Americ

In vivo potential hypoglycemic and in vitro vasorelaxant effects of Cecropia glazioviistandardized extracts

ABSTRACTThe aim of this study is to investigate the effect of Cecropia glaziovii Snethl, Urticaceae, extracts on the oral glucose tolerance curve, on glycemia in alloxan-induced diabetic rats and vasorelaxant effect after the extraction process, and to standardize the extractive solutions. The effects of the process variables and their interactions were calculated in relation to dry residue, pH, total phenolic results and chemical marker content. Furthermore, the effect of the extracts (400 mg/kg), chlorogenic (2 or 15 mg/kg) and caffeic acids (2 mg/kg) were investigated on the oral glucose tolerance curve and on glycemia in alloxan-induced diabetic rats. Oral administration of ethanol extracts 4d20 and 8d20 significantly improved glucose tolerance in the hyperglycemic rats. Chlorogenic and caffeic acids, as well as the association of the compounds were able to significantly reduce glycemia after oral gavage treatments. On the other hand, the aqueous extracts did not alter the glycemia. The aqueous extracts (8020 and 9030) and only the higher dose of chlorogenic acid presented a significant effect on serum glucose lowering in diabetic rats. Additionally, the IC50 reveals that the ethanol extracts presented more potent vasodilator effects than the aqueous extracts in aortic rings. This study shows that C. glazioviistandardized extracts exhibits antihyperglycemic action, is able to improve glucose tolerance and has a potent vascular relaxing effect. These results are probably linked to concentrations of the main phenolic compounds of the extracts

Development and effect of storage on the stability of enriched flavonoid fraction of <i>Cecropia glaziovii</i>-loaded PLGA nanoparticles

<p>Studies employing <i>Cecropia glaziovii</i> Snethl leaves have shown great potential in regard to their antiviral activity, mainly related to the phenolic compounds present in this species. The main goal of this work is to combine the therapeutic potential of this species with new technological strategies targeted at the development of an herbal nanoparticulate system for the preparation of a phytotherapeutic formulation. Poly (lactic-co-glycolic acid) nanoparticles containing the enriched flavonoid fraction of <i>Cecropia glaziovii</i> Snethl were developed through a study for the choice of preparation technique, amount of drug and surfactants used. These nanostructured systems were characterized by particle size, polydispersity, zeta potential, encapsulation efficiency and drug-loading capacity. A stability study of the formulations was conducted at room temperature over a period of 60 days. The optimal formulation that best fit the characteristics of the encapsulated material was determined. Sorbitan monooleate and the poloxamer 188 resulted in better colloidal stability, added to the organic and aqueous phases, respectively. These findings suggest that in the field of nanoparticles stability, it is important to evaluate the composition of the nanoparticulate system. This work highlights the importance of the optimization process, searching for a good formulation with suitable structural stabilization.</p