Long-lasting anti-platelet activity of cilostazol from poly(ε-caprolactone)-poly(ethylene glycol) blend nanocapsules.

Cilostazol (CLZ) acts as a vasodilator and antiplatelet agent and is the main drug for the treatment of intermittent claudication (IC) related to peripheral arterial disease (PAD). The usual oral dose is 100 mg twice a day, which represents a disadvantage in treatment compliance. CLZ presents several side effects, such as headache, runny nose, and dizziness. This paper aimed to obtain novel polymeric nanocapsules prepared from poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG) blend containing CLZ. Nanocapsules showed pH values between 6.1 and 6.3, average size lower than 137 nm, low polydispersity index (<0.22) and negative zeta potential. These nanoformulations demonstrated spherical shape with smooth surface. Results achieved by X-ray diffraction (XRD) and differential scanning calorimetry (DSC) indicated drug amorphization compared to pure CLZ. Fourier-transformed infrared spectroscopy (FTIR) showed no chemical bonds between drug and polymers. Formulations presented suitable stability for physical parameters. The in vitro drug release demonstrated prolonged release with no burst effect. Drug release was controlled by both mechanisms of polymer relaxation/degradation and Fickian diffusion. Moreover, chosen CLZ-loaded nanocapsules provided an in vivo prolonged antiplatelet effect for CLZ statistically similar to aspirin. These formulations can be further used as a feasible oral drug delivery carrier for controlled release of CLZ in order to treat PAD and IC events.

Chemical Composition and Biological Activities of The Essential Oil And Anatomical Markers Of Lavandula Dentata L. Cultivated In Brazil

ABSTRACT Lavandula dentata, popularly known as lavender, is commonly used in traditional medicine for the treatment of digestive and inflammatory disorders. The objective of this study was to analyzed the chemical oil composition, antioxidant and antimicrobial activities of the essential oil and anatomical markers of the leaf and stem of L. dentata cultivated in South Brazil. Essential oil showed an antioxidant activity similar to rutin and gallic acid when analyzed by phosphomolybdenum method. However, by the free radical DPPH and ABTS methods, it showed a slight potential antioxidant. Essential oil presented 1,8-cineol (63%) as major component, antimicrobial activity against Gram-positive, Gram-negative bacteria strains and Candida albicans, by broth microdilution. The anatomical profile provided the following main microscopic markers: hypostomatic leaves; diacytic stomata, thin and striate cuticle; multicellular and branched non-glandular trichomes; capitate glandular trichomes; peltate glandular trichomes; dorsiventral mesophyll; flat-convex shape midrib, truncated on the abaxial side; one collateral vascular bundle in the midrib; square stem shape, angular collenchyma alternated with cortical parenchyma; sclerenchymatic fibers well-developed on the four edges.

Cytotoxic mechanism of Baccharis milleflora (Less.) DC. essential oil.

The aim of this study was to investigate the cytotoxic activity of the essential oil from cladodes of Bacharis milleflora in relation to Jurkat, Raji and HL-60 cells, as well as exploring the cell mechanisms in order to elucidate how the cytotoxic process occurs. The presence of the following volatile compounds was detected by GC-MS: bicyclogermacrene (12.16%), germacrene D (11.18%), (E)-caryophyllene (9.28%), and α-humulene (8.05%). In general, IC50 values lower than 50µg/mL were obtained for all the tumor cells at 24, 48 and 72h by MTT assay. The decrease in cell DNA content was demonstrated due to the inhibition of the proliferation of Jurkat, Raji and HL-60 cells by B. milleflora essential oil. In particular, Raji cells presented the greatest inhibition of cell proliferation and they were subsequently used to investigate cell death mechanisms. B. milleflora essential oil promoted G0/G1 arrest and also induced cell fragmentation, which was represented by an increase in the sub-G0 population, indicating cell death induced by apoptosis. The selectivity index was 3.97. Necrotic cell death, coupled with low levels of apoptotic cell death, was observed by conventional EB/AO and Hoechst 33342 staining assays, demonstrating that this essential oil acts via both necrotic and apoptotic mechanisms.

Spray-dried solid dispersions containing ferulic acid: comparative analysis of three carriers, in vitro dissolution, antioxidant potential and in vivo anti-platelet effect.

This article aimed to improve the relative solubility and dissolution rate of ferulic acid (FA) by the use of spray-dried solid dispersions (SDs) in order to ensure its in vitro antioxidant potential and to enhance its in vivo anti-platelet effect. These SDs were prepared by spray-drying at 10 and 20% of drug concentration using polyvinylpyrrolidone K30 (PVP-K30), polyethylene glycol 6000 (PEG 6000) and poloxamer-188 (PLX-188) as carriers. SDs and physical mixtures (PM) were characterized by SEM, XRPD, FTIR spectroscopy and TGA analysis. Spray-dried SDs containing FA were successfully obtained. Relative solubility of FA was improved with increasing carrier concentration. PVP-K30 and PEG 6000 formulations showed suitable drug content values close to 100%, whereas PLX-188 presented mean values between 70 and 90%. Agglomerates were observed depending on the carrier used. XRPD patterns and thermograms indicated that spray-drying led to drug amorphization and provided appropriate thermal stability, respectively. FTIR spectra demonstrated no remarkable interaction between carrier and drug for PEG 6000 and PLX-188 SDs. PVP-K30 formulations had changes in FTIR spectra, which denoted intermolecular O-H•••O = C bonds. Spray-dried SDs played an important role in enhancing dissolution rate of FA when compared to pure drug. The free radical-scavenging assay confirmed that the antioxidant activity of PEG 6000 10% SDs was kept. This formulation also provided a statistically increased in vivo anti-platelet effect compared to pure drug. In summary, these formulations enhanced relative solubility and dissolution rate of FA and chosen formulation demonstrated suitable in vitro antioxidant activity and improved in vivo anti-platelet effect.

Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect.

This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3µm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects.

ATIVIDADE ANTIMICROBIANA DE MÉIS PRODUZIDOS POR MELIPONÍNEOS NATIVOS DO PARANÁ (BRASIL) / ANTIMICROBIAL ACTIVITY OF HONEYS PROVIDED BY MELIPONINES FROM PARANÁ (BRAZIL)

O objetivo deste trabalho foi estudar a atividade antibacteriana e antifúngica de méis in natura, elaborados por abelhas nativas sem ferrão e de extratos fenólicos (EFM) obtidos a partir dessas amostras. A atividade antimicrobiana de 21 amostras de mel, coletadas no Estado do Paraná (Brasil), foi avaliada pelo método de microdiluição em caldo, determinando-se a concentração inibitória mínima (MIC) contra as cepas de Escherichia coli ATCC 10530, Staphylococcus aureus ATCC 25923 e Candida albicans ATCC 10231. As amostras de mel apresentaram maior atividade antimicrobiana para as bactérias E. coli (MIC90 ≥3,12%) e S. aureus (MIC90 ≥1,56%) em comparação aos valores obtidos para a levedura C. albicans (MIC90 ≥12,5%). Os EFM revelaram menor atividade antimicrobiana em relação aos méis in natura, pois apenas nove amostras de EFM inibiram o crescimento de S. aureus em10 mg.mL­1. Tais resultados permitem inferir que o mel de abelhas sem ferrão constitui alimento com propriedades funcionais e que apresenta potencial terapêutico contra infecções.

Physicochemical quality control of bee honeysfrom Campos Gerais region of Paraná: Brazil

Bee (Apis mellifera L.) honeys have been widely used for therapeutic and nutritional proposes. For evaluating the honey production, physicochemical approaches have been extensively performed to ensure that this hive product is authentic in respect to the legal requirements. The aim of this paper was to discuss the quality control of 93 samples of honey from Campos Gerais region of Paraná State – South Brazil by physicochemical parameters. Moisture, reducing sugars, sucrose, water-insoluble solids, ash, free acidity, pH, activity of diastase, hydroxymethylfurfural content and colour were performed by the standard usual methods. Samples were also classified in floral honeys or honeydew honeys according to the Kirkwood equation. A total of 71 samples (76.34%) showed values in accordance with the Brazilian legal requirements for all the achieved physicochemical parameters. Otherwise, all the studied honeys were likewise within the legislation limits only for water-insoluble solids and colour. For pH, an additional parameter that has not been provided in honey legislation, samples showed values ranging from 3.60 to 5.35. By the Kirkwood equation, 61 honeys were considered as floral products.