Physicochemical characterization of the metamorphosis of film-forming formulations of betamethasone-17-valerate.

Following topical application of a dermatological product, the loss (by evaporation and/or absorption through the skin) of volatile excipients will alter the composition of the formulation remaining on the tissue. This so-called metamorphosis impacts the concentration of the drug in the residual vehicle, (potentially) its physical form therein and, as a result, its uptake into and subsequent permeation through the skin. This research aimed to characterise - using primarily confocal Raman microspectroscopy - the metamorphosis of film-forming formulations of betamethasone-17-valerate (at different loadings) comprised of hydroxypropyl cellulose (film-forming agent), triethyl citrate (plasticizer) and ethanol (solvent).

Assessment of dermal bioavailability: predicting the input function for topical glucocorticoids using stratum corneum sampling.

Predicting the dermal bioavailability of topically delivered drugs is challenging. In this work, minimally invasive stratum corneum (SC) sampling was used to quantify the delivery of betamethasone valerate (BMV) into the viable skin. Betnovate® cream (0.

Skin Pharmacokinetics of Transdermal Scopolamine: Measurements and Modeling.

Prediction of skin absorption and local bioavailability from topical formulations remains a difficult task. An important challenge in forecasting topical bioavailability is the limited information available about local and systemic drug concentrations post application of topical drug products. Commercially available transdermal patches, such as Scopoderm (Novartis Consumer Health UK), offer an opportunity to test these experimental approaches as systemic pharmacokinetic data are available with which to validate a predictive model.

Stratum Corneum Sampling to Assess Bioequivalence between Topical Acyclovir Products.

Purpose: To examine the potential of stratum corneum (SC) sampling via tape-stripping in humans to assess bioequivalence of topical acyclovir drug products, and to explore the potential value of alternative metrics of local skin bioavailability calculable from SC sampling experiments.

Methods: Three acyclovir creams were considered in two separate studies in which drug amounts in the SC after uptake and clearance periods were measured and used to assess bioequivalence. In each study, a "reference" formulation (evaluated twice) was compared to the "test" in 10 subjects.

Development and characterisation of chondroitin sulfate- and hyaluronic acid-incorporated sorbitan ester nanoparticles as gene delivery systems.

Glycosaminoglycans (GAGs) are natural polymers that are broadly used in gene delivery systems to increase stability as well as decrease toxicity and nonspecific interactions, thereby increasing transfection efficiency. In this work, we propose sorbitan ester-based lipid nanoparticles (SENS) functionalised with the GAGs chondroitin sulfate (CS) and hyaluronic acid (HA) as gene delivery systems. For this purpose, we describe the design and evaluation of these nanosystems loaded with plasmid DNA, including an evaluation of their physicochemical characteristics, stability properties, ability to protect and efficiently transfect cells with Enhanced Green Fluorescent Protein plasmid (pEGFP) in vitro, and biocompatibility both in vitro and in vivo.

Topical bioavailability of diclofenac from locally-acting, dermatological formulations.

Assessment of the bioavailability of topically applied drugs designed to act within or beneath the skin is a challenging objective. A number of different, but potentially complementary, techniques are under evaluation. The objective of this work was to evaluate in vitro skin penetration and stratum corneum tape-stripping in vivo as tools with which to measure topical diclofenac bioavailability from three approved and commercialized products (two gels and one solution).

Influence of Fluorination on the Solubilities of Carbon Dioxide, Ethane, and Nitrogen in 1-n-Fluoro-alkyl-3-methylimidazolium Bis(n-fluoroalkylsulfonyl)amide Ionic Liquids.

The effect on gas solubilities of adding partially fluorinated alkyl side chains either on imidazolium-based cations or on bis(perfluoroalkylsulfonyl)amide anions was studied. The aim was to gain knowledge of the mechanisms of dissolution of gases in fluorinated ionic liquids and, if possible, to improve physical absorption of carbon dioxide in ionic liquids. We have determined experimentally, in the temperature range of 298-343 K and at pressures close to atmospheric pressure, the solubility and thermodynamics of solvation of carbon dioxide, ethane, and nitrogen in the ionic liquids 1-octyl-3-methylimidazolium bis[trifluoromethylsulfonyl]amide ([Cmim][NTf]), 1-octyl-3-methylimidazolium bis[pentafluoroethylsulfonyl]amide ([Cmim][BETI]), 1-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-3-methylimidazolium bis[trifluoromethylsulfonyl]amide ([CHFmim][NTf]), and 1-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-3-methylimidazolium bis[pentafluoroethylsulfonyl]amide ([CHFmim][BETI]).

Span poly-L-arginine nanoparticles are efficient non-viral vectors for PRPF31 gene delivery: An approach of gene therapy to treat retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common cause of inherited blindness in adults. Mutations in the PRPF31 gene produce autosomal dominant RP (adRP). To date there are no effective treatments for this disease.

Structural analysis of nanosystems: Solid Sorbitan esters Nanoparticles (SSN) as a case study.

Innovative approaches in nanotechnology can provide drug delivery systems with a high potential in different fields. To avoid trial and error assays as a main driving force governing new designs and, furthermore, to develop successful nanosystem optimization strategies, it is of the greatest importance to develop specific characterisation techniques beyond conventional determinations of size, zeta potential and morphology. However, the application of techniques able to determine some key characteristics, such as nanostructure (i.

Characterization and comparison of two novel nanosystems associated with siRNA for cellular therapy.

To direct stem cell fate, a delicate control of gene expression through small interference RNA (siRNA) is emerging as a new and safe promising strategy. In this way, the expression of proteins hindering neuronal commitment may be transiently inhibited thus driving differentiation. Mesenchymal stem cells (MSC), which secrete tissue repair factors, possess immunomodulatory properties and may differentiate towards the neuronal lineage, are a promising cell source for cell therapy studies in the central nervous system.

Rationale and study design for an individualized perioperative open lung ventilatory strategy (iPROVE): study protocol for a randomized controlled trial.

Background: Postoperative pulmonary and non-pulmonary complications are common problems that increase morbidity and mortality in surgical patients, even though the incidence has decreased with the increased use of protective lung ventilation strategies. Previous trials have focused on standard strategies in the intraoperative or postoperative period, but without personalizing these strategies to suit the needs of each individual patient and without considering both these periods as a global perioperative lung-protective approach. The trial presented here aims at comparing postoperative complications when using an individualized ventilatory management strategy in the intraoperative and immediate postoperative periods with those when using a standard protective ventilation strategy in patients scheduled for major abdominal surgery.

Anionic nanoparticles based on Span 80 as low-cost, simple and efficient non-viral gene-transfection systems.

The existing strategies in the design of non-viral vectors for gene therapy are primarily conceived for cationic systems. However, the safety concerns associated with the use of positively charged systems for nucleic acid delivery and several reports regarding the efficacy of negatively charged systems highlights the need for improved gene-delivery vectors. With these premises in mind, we investigated the development of new negatively charged nanoparticles based on Sorbitan esters (Span(®)) – extremely cheap excipients broadly used in the pharmaceutical industry – on the basis of a simple, one-step and easily scalable procedure.

Current strategies for DNA therapy based on lipid nanocarriers.

Introduction: Lipid based nanocarriers represent one of the most widely used strategies for the delivery of gene molecules. This review focuses on current strategies for the use of these nanocarriers that could open new horizons in DNA therapy and offer an opportunity to support the transition from resource-based approaches towards knowledge-based strategies.

Areas Covered: The present review highlights the most promising approaches focusing on the development of safe, stable, and effective lipid-based carriers capable of delivering DNA to the proper target sites and cells.

A theoretical and experimental chemist's joint view on hydrogen bonding in ionic liquids and their binary mixtures.

A combined experimental and theoretical approach including quantum chemistry tools and computational simulation techniques can provide a holistic description of the nature of the interactions present in ionic liquid media. The nature of hydrogen bonding in ionic liquids is an especially intriguing aspect, and it is affected by all types of interactions occurring in this media. Overall, these interactions represent a delicate balance of forces that influence the structure and dynamics, and hence the properties of ionic liquids.

Bulk and liquid-vapor interface of pyrrolidinium-based ionic liquids: a molecular simulation study.

Using molecular dynamics simulations, we have studied the structure of three 1-butyl-1-methylpyrrolidinium ionic liquids whose anions are triflate, bis(trifluoromethanesulfonyl)imide, and tris(pentafluoroethyl)trifluorophosphate. The structure of the bulk phase of the three ionic liquids has been interpreted using radial and spatial distribution functions and structure factors that allows us to characterize the morphology of the polar and nonpolar domains present in this family of liquids. The size of the polar regions depends on the anion size, whereas the morphology of the nonpolar domains is anion-independent.

Understanding the evaporation of ionic liquids using the example of 1-ethyl-3-methylimidazolium ethylsulfate.

In this work we present a comprehensive temperature-dependence analysis of both the structural and the dynamic properties of a vaporized ionic liquid (1-ethyl-3-methylimidazolium ethylsulfate). This particular ionic liquid is known to be distillable from experimental studies and thus enables us to deepen the understanding of the evaporation mechanism of ionic liquids. We have used ab initio molecular dynamics of one ion pair at three different temperatures to accurately describe the interactions present in this model ionic liquid.

Side chain fluorination and anion effect on the structure of 1-butyl-3-methylimidazolium ionic liquids.

We present a comprehensive molecular dynamics simulation study on 1-butyl-3-methylimidazolium ionic liquids and their fluorinated analogs. The work focused on the effect of fluorination at varying anions. The main findings are that the fluorination of the cations side chain increases overall structuring, especially the aggregation of cation side chain.

Using molecular simulation to understand the structure of [C2C1im]+-alkylsulfate ionic liquids: bulk and liquid-vapor interfaces.

Using molecular dynamics simulations we have studied the structure of alkylsulfate-based ionic liquids: 1-ethyl-3-methylimidazolium n-alkylsulfate [C(2)C(1)im][C(n)SO(4)] (n = 2, 4, 6 and 8). The structure of the different ionic liquids have been interpreted taking into account radial and spatial distribution functions, and structure factors, that allowed us to characterize the morphology of the polar and nonpolar domains present in this family of liquids. The size of the nonpolar regions depends linearly on the anion alkyl chain length.

On the ideality of binary mixtures of ionic liquids.

In this work, structural and dynamical properties of the binary mixture of 1-ethyl-3-methyl-imidazolium chloride and 1-ethyl-3-methyl-imidazolium thiocyanate are investigated from ab initio molecular dynamics simulations and compared to the pure ionic liquids. Furthermore, the binary mixture is simulated with two different densities to gain insight into how the selected density affects the different properties. In addition, a simple NMR experiment is carried out to investigate the changes of the chemical shifts of the hydrogen atoms due to the composition of the mixture.

The bulk and the gas phase of 1-ethyl-3-methylimidazolium ethylsulfate: dispersion interaction makes the difference.

Ab initio molecular dynamics simulations were carried out on systems representing the gas and the bulk phase of 1-ethyl-3-methylimidazolium ethylsulfate [C(2)C(1)im][C(2)SO(4)]. The power spectra and cation-anion spatial distribution revealed different interactions of the anion and cation in the bulk phase versus the gas phase. In the bulk phase, all oxygen atoms of the anions are involved and interaction via the rear hydrogen atoms is possible, forming a closer packed system.

On the density scaling of pVT data and transport properties for molecular and ionic liquids.

In this work, a general equation of state (EOS) recently derived by Grzybowski et al. [Phys. Rev.

Absorption of carbon dioxide, nitrous oxide, ethane and nitrogen by 1-alkyl-3-methylimidazolium (C(n)mim, n = 2,4,6) tris(pentafluoroethyl)trifluorophosphate ionic liquids (eFAP).

We measured the densities of 1-alkyl-3-methylimidazolium (C(n)mim, n = 2,4,6) tris(pentafluoroethyl)trifluorophosphate ionic liquids (eFAP) as a function of temperature and pressure and their viscosities as a function of temperature. These ionic liquids are less viscous than those based in the same cations but with other anions such as bis(trifluoromethylsulfonyl)imide. The ionic liquids studied are only partially miscible with water, their solubility increasing with the size of the alkyl side-chain of the cation and with temperature (from x(H(2)O) = 0.

[Spanish Society of Anaesthesia (SEDAR) guidelines for pre-anaesthesia checking procedures].

We present this document as a guide to preparing a specific institutional pre-anaesthesia checklist, as recommended in the Helsinki declaration on patient safety in anaesthesiology. Also, the recently recommended WHO "safe surgery check-list" includes a check-list for anaesthesia. A working group was established in accordance with the charter of the Spanish Society of Anaesthesiology and Resuscitation (Sociedad Española de Anestesiología y Reanimación [SEDAR]).

2D or not 2D: structural and charge ordering at the solid-liquid interface of the 1-(2-hydroxyethyl)-3-methylimidazolium tetrafluoroborate ionic liquid.

Molecular dynamics simulations of a 5 nm-thick layer of the ionic liquid 1-(2-hydroxyethyl)-3-methylimidazolium tetrafluoroborate, [(OH)C2C1im][BF4], over silica, alumina and boro-silicate glass substrates have been performed. The structure of the ionic liquid at the solid-liquid interface has been interpreted taking into account the corresponding normal density profiles, lateral interfacial structure, orientational ordering and planar density contours. Comparisons with experimental data suggest that the adsorption and stratification process of ionic liquids over solid substrates can be correctly modeled using a realistic rendition of a non-uniform amorphous substrate such as a glass material.