Influence of phospholipid composition on cationic emulsions/DNA complexes: physicochemical properties, cytotoxicity, and transfection on Hep G2 cells

Michelle Fraga1,2, Fernanda Bruxel1, Valeska Lizzi Lagranha2,3, Helder Ferreira Teixeira1, Ursula Matte2,31Post Graduation Program in Pharmaceutical Sciences, Universidade Federal do Rio Grande do Sul, 2Gene Therapy Center, Experimental Research Center, Hospital de Clínicas de Porto Alegre, 3Post Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilBackground: Cationic nanoemulsions have been recently considered as potential delivery systems for nucleic acids. This study reports the influence of phospholipids on the properties of cationic nanoemulsions/DNA plasmid complexes.Methods: Nanoemulsions composed of medium-chain triglycerides, stearylamine, egg lecithin or isolated phospholipids, ie, DSPC, DOPC, DSPE, or DOPE, glycerol, and water were prepared by spontaneous emulsification. Gene transfer to Hep G2 cells was analyzed using real-time polymerase chain reaction.Results: The procedure resulted in monodispersed nanoemulsions with a droplet size and zeta potential of approximately 250 nm and +50 mV, respectively. The complexation of cationic nanoemulsions with DNA plasmid, analyzed by agarose gel retardation assay, was complete when the complex was obtained at a charge ratio of ≥1.0. In these conditions, the complexes were protected from enzymatic degradation by DNase I. The cytotoxicity of the complexes in Hep G2 cells, evaluated by MTT assay, showed that an increasing number of complexes led to progressive toxicity. Higher amounts of reporter DNA were detected for the formulation obtained with the DSPC phospholipid. Complexes containing DSPC and DSPE phospholipids, which have high phase transition temperatures, were less toxic in comparison with the formulations obtained with lecithin, DOPC, and DOPE.Conclusion: The results show the effect of the DNA/nanoemulsion complexes composition on the toxicity and transfection results.Keywords: plasmids, cationic nanoemulsions, phospholipids, physicochemical characterization, gene transfer, stearylamin

Administração da dívida pública sob um regime de metas para inflação: evidências para o caso brasileiro

A utilização da taxa de juros como principal instrumento para a obtenção da meta de inflação e o fato de grande parte da dívida pública brasileira estar indexada a essa taxa faz com que haja uma reciprocidade entre a condução da política monetária e o gerenciamento da dívida pública. Foi observado que o uso da política monetária voltada para um processo de desinflação provocou um efeito negativo que não pode ser negligenciado para o equilíbrio fiscal. Os resultados indicam que a estratégia de aumentar a participação de títulos prefixados e indexados ao índice de preços mostra-se adequada para evitar uma deterioração na razão dívida/PIB. Por outro lado, a ampliação do prazo médio da dívida pública ainda não trouxe os benefícios esperados. Uma variável que merece atenção é a credibilidade na condução da política monetária, uma vez que ela é capaz de contribuir tanto para uma redução na dívida pública quanto para o controle da inflação.The use of the interest rate as the main instrument in the search for inflation target and the fact that large part of the Brazilian public debt is indexed to this rate implies a reciprocity between the conduction of monetary policy and public debt management. It was observed that the use of the monetary policy focused on a disinflationary process implied a negative effect that cannot be neglect for the fiscal equilibrium. The findings denote that the strategy of increasing the share of prefixed public bonds and indexed to the price index is adequate to avoid deterioration in the public debt/GDP ratio. On the other hand, an increase in the average maturity of public debt still not provoked the expected advantages. A variable that deserves attention is the credibility in the conduction of the monetary policy because it is capable to promote a fall in the public debt and improves the control on inflation

Development of nanoemulsions containing penciclovir for herpes simplex treatment and a liquid chromatographic method to drug assessment in porcine skin layers

A successful formulation (penciclovir hydrogel nanoemulsion - HN) to be used in transdermal drug delivery route to treat herpes simplex virus was developed and an analytical method to quantify penciclovir (PCV) in porcine ear skin was stablished and validated. PCV nanoemulsions were prepared by high pressure homogenization and presented spherical mean droplet size 180 nm. The association efficiency and zeta potential were 87% and– 27 mV, respectively. The bioanalytical method developed showed specificity for the interferences from the skin matrixes (epidermis and dermis) and the linearity was in the range 0.1 – 25 μg/mL of drug, The mean recovery data for the three levels tested were 95.2% for the epidermis and 97.3% for the dermis and adequate results were obtained for repeatability and inter-day precision.  In vitro percutaneous absorption studies with the PCV nanoemulsion and a market cream were conducted employing the porcine skin.The cumulative amounts of PCV permeated from cream and HN, 8 h after dosing, were 2.60 and 4.15 μg/cm², respectively, representing a quite higher flux and a much higher permeability coefficient for the developed formulation. It can be concluded that HN provide a good skin targeting effect and may be a promising carrier for topical delivery of penciclovir

Impact of aquatic-based physical exercise programmes on risk markers of cardiometabolic diseases in old people: a study protocol of randomized-controlled trials

Cardiometabolic diseases are one of the primary causes of mortality and morbidity worldwide and sedentary lifestyles are contributing factors to these pathologies. Physical exercise has been recognized as an important tool in the prevention and treatment of these diseases. However, there are still some doubts about the efficacy of certain type of physical exercise programs for older participants. The main goal of this study is to assess the impact of different aquatic-based physical exercise programs on risk markers of cardiometabolic diseases in older people. The study group will consist of non-institutionalized individuals, within the age group of 65 or older. The sample will be randomly divided into four groups, three experimental groups (EG) and one control group (CG). Participants fromthe EGs will be exposed to three physical aquatic-based exercise programs for a period of 28 weeks (continuous aerobic, interval aerobic and combined). The evaluated parameters include anthropometry, physical functions, mental health, cognitive function, carotid arteries intima-media thickness, heart rate variability and biochemical markers. The results will allow an interpretation of the impact of different aquatic-based physical exercise programs on cardiometabolic diseases markers and can also be used as a tool for professionals to prescribe adequate and more efficient physical exercise programs.info:eu-repo/semantics/publishedVersio

Improved skin delivery and validation of novel stability-indicating HPLC method for ketoprofen nanoemulsion

Abstract Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) widely used to treat rheumatoid arthritis and other inflammatory diseases. Normally used by oral route, this drug presents numerous side effects related to this administration route, such as nausea, dyspepsia, diarrhea, constipation and even renal complications. To avoid that, topical administration of ketoprofen represents a good alternative, since this drug has both partition coefficient and aqueous solubility suitable for skin application, compared to other NSAIDs. In this study, we describe the production of a nanoemulsion containing ketoprofen, its skin permeation and in vitro release study and a novel validation method to analyze this drug in the permeation samples and a forced degradation study using skin and nanoemulsion samples. The new HPLC method was validated, with all specifications in accordance with validation parameters and with an easy chromatographic condition. Forced degradation study revealed that ketoprofen is sensitive to acid and basic hydrolysis, developing degradation peaks after exposure to these factors. Concerning in vitro release from the nanoemulsion, release curves presented first order profile and were not similar to each other. After 8 h, 85% of ketoprofen was release from the nanoemulsion matrix while 49% was release from control group. In skin permeation study, nanoemulsion enabled ketoprofen to pass through the skin and enhanced retention in the epidermis and stratum corneum, layer on which the formulation presented statistically different values compared to the control group

Cyclodextrin-based delivery systems and hydroxycinnamic acids : interactions and effects on crucial parameters influencing oral bioavailability — aReview

Hydroxycinnamic acids (HCAs) are a subclass of phenolic acids presenting caffeic acid (CA), chlorogenic acid (CGA), coumaric acid (COA) isomers, ferulic acid (FA), and rosmarinic acid (RA) as the major representants, being broadly distributed into vegetal species and showing a range of biological potentials. Due to the low oral bioavailability of the HCAs, the development of delivery systems to promote better administration by the oral route is demanding. Among the systems, cyclodextrin (CD)-based delivery systems emerge as an important technology to solve this issue. Regarding these aspects, in this review, CD-based delivery systems containing HCAs are displayed, described, and discussed concerning the degree of interaction and their effects on crucial parameters that affect the oral bioavailability of HCAs