Nanostructured lipid carriers loaded with essential oils: a strategy against SARS-CoV-2.

This work aimed to investigate the effectiveness of Lippia sidoides and Syzygium aromaticum essential oils (EOs) encapsulated in nanostructured lipid carriers (NLCs) as SARS-CoV-2 inhibitors through virucidal activity assessment. We developed anionic and cationic NLCs loaded with the EOs and assessed their physicochemical properties and SARS-CoV-2 virucidal activity, focusing on the effects of EO type and the NLCs composition. The NLCs exhibited particle sizes of 141.30 to 160.53 nm for anionic and 109.30 to 138.60 nm for cationic types, with PDIs between 0.16 and 0.25. High zeta potentials (>29.0 in modulus) indicated stable formulations. The NLCs effectively encapsulated the EOs, achieving encapsulation efficiencies between 84.6 to 100% w/w of marker compound. The EOs-loaded NLCs reduced the SARS-CoV-2 virion count, exceeding 2 logs over the control. NLCs loaded with Lippia sidoides and Syzygium aromaticum EOs represent an innovative strategy for combating SARS-CoV-2.

Influência do processo de secagem e condição de armazenamento de extratos secos de Bauhinia forficata e Passiflora alata sobre seu perfil de dissolução / Influence of the drying process and storage condition on the dissolution behavior of dried extracts of Bauhinia forficata and Passiflora alata

No Brasil, os produtos fitoterápicos são considerados medicamentos, sendo necessário o estabelecimento de estudos que assegurem a manutenção dos requisitos de qualidade durante o processamento e o armazenamento. Testes de dissolução podem ser empregados para se estimar a biodisponibilidade de um fármaco, sendo uma análise rotineira no desenvolvimento e controle de qualidade de medicamentos alopáticos. A determinação do perfil de dissolução de fitoterápicos também pode ser um importante critério para avaliação da sua qualidade lote-a-lote, bem como para os estudos de desenvolvimento e de estabilidade. O objetivo deste trabalho foi investigar a influência dos métodos de secagem e da condição de armazenagem sobre os perfis de dissolução dos flavonoides totais de extratos secos de duas plantas medicinais bastante difundidas no Brasil, a Bauhinia forficata e a Passiflora alata. Os extratos secos foram produzidos pelo processo de secagem em leito de jorro e em spray drying, sendo submetidos a condições de armazenagem aceleradas (temperatura de 40 ± 2ºC e umidade relativa de 75 ± 5%, por um período de 90 dias). Os perfis de dissolução foram obtidos para amostras de extratos secos antes e após o período de armazenamento. O teor de flavonoides totais foi quantificado por espectrofotometria. Os extratos secos de B. forficata e P. alata apresentaram adequada liberação de flavonoides nos ensaios de dissolução. Os extratos secos de Passiflora alata apresentaram completa dissolução dos flavonoides, 92% e 98% dos teores originais após 60 minutos de ensaio, respectivamente para o extrato seco em leito de jorro e em spray drying.

In Brazil, most of the herbal medicinal products are considered as medicine. Therefore, it is necessary the establishment of tests to guarantee the maintenance of quality requirements during their processing and storage. The dissolution test is used to estimate the bioavailability of drugs and is routinely used in the development and the quality control of allopathic medicines. The determination of the dissolution profile of herbal products can also be an important criterion for assessing the batch-to-batch quality as well as for studies of product development and stability. This work aimed to investigate the dissolution profiles of dried extracts of two medicinal plants widely used in Brazil, the Bauhinia forficata and Passiflora alata, by assessing the effect of the drying methods and storage condition on the release of the total flavonoid contents. Spouted bed and spray drying were the processes used for the production of the dried extracts. The products were subjected to accelerated storage conditions (temperature of 40 ± 2ºC and relative humidity of 75 ± 5%, for 90 days). The dissolution profiles of the dried extracts, before and after storage, were determined. The concentration of total flavonoids was quantified by spectrophotometry. Adequate dissolution profiles of flavonoids from B. forficata and P. alata were obtained for all the dried extracts produced. The dried extracts of Passiflora alata showed the complete dissolution of flavonoids in the dissolution media investigated, respectively 92% and 98% of flavonoids present in the dried extracts in spouted bed and spray drying after 60 minutes of the dissolution testing.

Assessment of antioxidant activity of spray dried extracts of Psidium guajava leaves by DPPH and chemiluminescence inhibition in human neutrophils.

This work evaluated the physicochemical properties and antioxidant activity of spray dried extracts (SDE) from Psidium guajava L. leaves. Different drying carriers, namely, maltodextrin, colloidal silicon dioxide, Arabic gum, and ß -cyclodextrin at concentrations of 40 and 80% relative to solids content, were added to drying composition. SDE were characterized through determination of the total phenolic, tannins, and flavonoid content. Antioxidant potential of the SDE was assessed by two assays: cellular test that measures the luminol-enhanced chemiluminescence (LumCL) produced by neutrophils stimulated with phorbol myristate acetate (PMA) and the DPPH radical scavenging (DPPH∗ method). In both assays the antioxidant activity of the SDE occurred in a concentration-dependent manner and showed no toxicity to the cells. Using the CLlum method, the IC50 ranged from 5.42 to 6.50 µg/mL. The IC50 of the SDE ranged from 7.96 to 8.11 µg/mL using the DPPH(•) method. Psidium guajava SDE presented significant antioxidant activity; thus they show high potential as an active phytopharmaceutical ingredient. Our findings in human neutrophils are pharmacologically relevant since they indicate that P. guajava SDE is a potential antioxidant and anti-inflammatory agent in human cells.

Níveis de cromo orgânico em rações para frangos de corte mantidos sob estresse por calor no período de um a 42 dias de idade / Levels of dietary chromiumin rations for male broilers kept under heat stress from one to 42 days of age

Avaliou-se o efeito da suplementação de cromo sobre o desempenho e o rendimento de cortes de frangos, mantidos em ambiente de alta temperatura, no período de um a 42 dias de idade. Foram utilizados 400 frangos de corte, machos, da linhagem Cobb, em um delineamento experimental inteiramente ao acaso, com cinco tratamentos, 0, 350, 700, 1.050 e 1.400ppb de cromo na ração, oito repetições e 10 aves por repetição. Nos períodos de um a 21 e de um a 42 dias de idade, não houve influência dos tratamentos sobre o ganho de peso, o consumo de ração e a conversão alimentar das aves, mas observou-se que o consumo de cromo aumentou de forma linear. Os tratamentos não influenciaram os pesos absoluto e relativo de nenhum dos cortes, peito, coxa e sobrecoxa, avaliados aos 42 dias de idade. A suplementação de até 1.400ppb de cromo na ração não influenciou o desempenho e o rendimento de cortes nobres de frangos de corte mantidos em estresse por calor, no período de um a 42 dias de idade.

The effect of dietary organic chromium supplementation on the performance and yield of prime cuts of male broilers from one to 42 days of age reared under high environmental temperature was evaluated. Four-hundred Cobb male broilers, averaging 38±0.14g were distributed in a simple sample random design with five treatments (0; 350; 700; 1,050; and 1,400ppb of chromium in ration), eight replicates, and ten birds per replicates. In periods from one to 21 and from one to 42 days of age, the treatments did not influence the weight gain, the food intake, and the feed:gain ratio of the birds. However, the chromium intake increased in a linear way. No effect of both absolute and relative weights of all evaluated cuts (breast, thigh, and drumstick) was observed. The dietary chromium supplementation up to 1,400ppb did not influence the performance and the carcass traits of the male broilers kept under heat stress from one to 42 days of age.

Influence of PEG-12 Dimethicone addition on stability and formation of emulsions containing liquid crystal.

Oil/water emulsions, containing liquid crystals, were developed employing Andiroba oil, PEG-12 Dimethicone and Crodafos CES. It was evaluated the influence of silicone surfactants on the emulsions stability and on the formation of liquid crystalline phases and therefore, physicochemical characteristics, such as rheology and zeta potential, were evaluated. Emulsions were prepared by the emulsions phase inversion method. All the formulations presented lamellar liquid crystalline phases. The PEG-12 Dimethicone addition did not change microscopically the liquid crystalline phases. The emulsions containing silicone demonstrated lower viscosity than those without the additive. This is an important feature, as the silicone did not change the rheological profile; however, the addition of silicone still can be used as a viscosity controller. The formulations had their viscosity increased 15 and 150 days after their preparation. This characteristic shows that the emulsions have their organization increased along the storing time. In the analysis of zeta potential, we could verify that all formulations presented negative values between -39.7 and -70.0 mV. Within this range of values, the emulsion physical stability is high (Fig. 10). It was concluded that the addition of PEG-12 Dimethicone kept the liquid crystalline phase of the emulsion obtained with Crodafos CES, influencing in a positive way in the system stability.

In vitro dissolution studies of sodium diclofenac granules coated with Eudragit L-30D-55 by fluidized-bed system.

The objective of this work was to study the dissolution process of sodium diclofenac granules coated with a polymeric suspension of Eudragit L-30D-55 by fluidized bed. Methacrylic acid-methylmetacrylate copolymer, also known as Eudragit, has been used as a pH sensitive coating material to protect drug substances prior to delivery to the human intestines. The sodium diclofenac granules were prepared by wet granulation technology using microcrystalline cellulose (MICROCEL), sodium diclofenac, and polivinilpirrolidone K-30. The granules coating operation was carried out in a fluidized bed with top spraying by a double-fluid nozzle. The dissolutions studies of the coated granules were performed in triplicate in a dissolution test station according to USP XXIII (1995) "in vitro testing requirements" Method A (paddle method, rotation of 100 RPM and temperature fixed at 37 degrees C). The dissolution mediums were 0.1N HCl solution and a pH 6.8 phosphate buffer solution, following the pH change dissolution procedure specified in USP for enteric-coated articles: 2 h of exposure to 750 mL of 0.1N HCl followed by testing in 1000 mL of pH 6.8 phosphate buffer, the pH being adjusted with 250 mL of 0.2 M tribasic sodium phosphate solution. The released amount of sodium diclofenac was periodically determined by UV spectrophotometry at wavelength of 276 nm, using a spectrophotometer UV-VIS HP 8453. The coated product showed gastric resistance properties confirming the feasibility of the fluidized bed for applying enteric coating in granules and pharmaceutical powders.

O/w dispersions development containing liquid crystals.

Liquid crystals are defined as the intermediary state between solid and liquid and also called of mesomorphous phase or crystalline phase, presenting characteristics of the mentioned physical states. For the simple emulsions that intermediary phase can act as forms of encapsulation of drugs providing its controlled liberation and besides, it can increase cutaneous hydration. These characteristics evidences the differentiation of the developed formulations and the use of the same ones in the release of new cosmetic vehicles. In that research we use vegetable oils (coffee, tomato), mineral oil, surfactants like phosphorics esthers (fractions A and B) and distilled water as aqueous phase. The stable formulations were submitted to stability physic-chemical preliminary tests (pH values determination, electric conductivity values, centrifugation and thermal stress) and later the compositions were submitted to accelerated stability tests (cold-hot cycle in the following temperature conditions--4 +/- 2 degrees C, 25 +/- 2 degrees C and 45 +/- 2 degrees C). Crystalline phase was identified by microscopy polarization. The recently prepared formulations and aged formulations (after 30 days) were appraised for rheology.

Evaluation of the anti-ulcerogenic activity of a dry extract of Maytenus ilicifolia Martius ex. Reiss produced by a jet spouted bed dryer.

We undertook the present study to evaluate the activity of the dried extract of Maytenus ilicifolia against stomach ulcers and in the increase of the volume and pH of the gastric juice of Wistar rats, as a model to evaluate the viability of the Jet Spouted Bed Dryer for the production of dry-extracts of medicinal Brazilian plants. The extract was obtained from the drying of a hydro-alcoholic extract with drying aid (40% of colloidal SiO2 related to solid content in the concentrated extract, at a concentration of 15.82% in water). The drying conditions employed were: Temperature of the spouting gas 150 degrees C, feed flow-rate of hydro-alcoholic extract 16.0 g/min, feed flow rate of the spouting gas 1.67 m3/min and static bed height 7.0 cm. Wistar rats received three different doses (140, 280 and 420 mg/kg) of the dried extract by intraperitoneal way and, after 60 minutes, were immobilized with wire screen and placed at temperature of 4 degrees C for two hours (cold-restraint stress). The animals were sacrificed and the stomach removed, examined and the volume and pH of the gastric secretion determined. A significant reduction in the ulceration index, was observed as well as a significant increase of the volume and of the pH of the gastric secretion for all doses administered. This is an indication that the preparation of dried extracts by the Jet spouted bed technique does not alter the biological activity of Maytenus ilicifolia.

Evaluation of the tablet coating by the conventional spouted-bed process.

The purpose of this paper was to present an analysis of the tablet coating by the conventional spouted-bed process. To analyze the equipment performance, the rate of increase of the tablets mass, K1, and the adhesion coefficient eta were determined as a function of the feed flow rate of coating suspension Ws; of the Reynolds number Rep; of the flow rate of atomizing gas Wat, and of the cone base angle gamma. To analyze the product quality, the uniformity of coating mass deposition onto the tablet's surface was used. Three different procedures for description of kinetics growth, weighing method, image analysis, and measurements with a micrometer were used to verify the validity of the commonly used weighing method. Comparison between experimental results of kinetics growth with estimates obtained by a literature model was also performed. A tendency toward an increase in K1 and in eta with the feeding flow rate of coating suspension Ws was detected. The weighing method can be used for the process analysis. The kinetics of growth can be described by the growth model used. The variable that produce more pronounced effect on K1 and eta was the feed flow rate of coating suspension, the weighing method describes very well the increase of particle diameter with coating time, the growth model can be used for the describe the kinetics of growth during the coating operation, and the coating does not deposit uniformly onto the tablet's surface.

Disaccharidase levels in normal epithelium of the small intestine of rats with iron-deficiency anemia.

Iron-deficiency anemia is the nutritional deficiency most frequently occurring throughout the world, which manifests as a complex systemic disease involving all cells, affecting enzyme activities and modifying protein synthesis. In view of these considerations, the objective of the present study was to determine the effects of iron-deficiency anemia on disaccharidases and on the epithelial morphokinetics of the jejunal mucosa. Newly weaned male Wistar rats were divided into 4 groups of 10 animals each: C6w received a standard ration containing 36 mg elemental iron per kg ration for 6 weeks; E6w received an iron-poor ration (5-8 mg/kg ration) for 6 weeks; C10w received an iron-rich ration (36 mg/kg ration) for 10 weeks; E10w received an iron-poor ration for 6 weeks and then an iron-rich ration (36 mg/kg) for an additional 4 weeks. Jejunal fragments were used to measure disaccharidase content and to study cell proliferation. The following results were obtained: 1) a significant reduction (P < 0.001) of animal weight, hemoglobin (Hb), serum iron and total iron-binding capacity (TIBC) in group E6w as compared to C6w; reversal of the alterations in Hb, serum iron and TIBC with iron repletion (E10w = C10w); animal weights continued to be significantly different in groups E10w and C10w. 2) Sucrase and maltase levels were unchanged; total and specific lactase levels were significantly lower in group E6w and this reduction was reversed by iron repletion (E10w = C10w). 3) The cell proliferation parameters did not differ between groups. On the basis of these results, we conclude that lactase production was influenced by iron deficiency and that this fact was not related to changes in cell population and proliferation in the intestinal mucosa.

Disaccharidase levels in normal epithelium of the small intestine of rats with iron-deficiency anemia

Iron-deficiency anemia is the nutritional deficiency most frequently occurring throughout the world, which manifests as a complex systemic disease involving all cells, affecting enzyme activities and modifying protein synthesis. In view of these considerations, the objective of the present study was to determine the effects of iron-deficiency anemia on disaccharidase and on the epithelial morphokinetics of the jejunal mucosa. Newly weaned male Wistar rats were divided into 4 groups of 10 animals each: C6w received a standard ration containing 36 mg elemental iron per Kg ration for 6 weeks; E6w received and iron-poor ration (5-8 mg/kg ration) for 6 weeks; C10w received an iron-rich ration (36 mg/kg ration) for 10 weeks; E10w received an iron-poor ration for 6 weeks and then an iron-rick ration (36 mg/kg) for an additional 4 weeks. Jejunal fragments were used to measure disaccharidase content and to study cell proliferation. The following results were obtained: 1) a significant reduction (P<0.001) of animal weight, hemoglobin (Hb), serum iron and total iron-binding capacity (TIBC) in groups E6w as compared to C6w; reversal of the alterations in Hb, serum iron and TIBC with iron repletion (E10w = C10w); animal weights continued to be significanly different in group E10w and C10w. 2) Sucrase and maltase levels were unchanged; total and specific lactase levels were significantly lower in group E6w and this reduction was reversed by iron repletion (E10w = C10w). 3) The cell proliferation parameters did not differ between groups. On the basis of these results, we conclude that lactase production was influenced by iron deficiency and that fact was not related to changes in cell population and proliferation in the intestinal mucosa.