Stability of an ophthalmic micellar formulation of cyclosporine A in unopened multidose eyedroppers and in simulated use conditions.

Cyclosporine A eye drops are used at concentrations ranging from 0.5 to 20mg/mL to treat a variety of ophthalmic diseases. Cyclosporine A formulations at high concentrations are difficult to manufacture because of cyclosporine's lipophilicity, and generally require an oil based vector. In this study, we investigated the physicochemical and microbiological stability of two high concentrations (10mg/mL and 20mg/mL) of an ophthalmic cyclosporine A micellar solution in a low density polyethylene multidose eyedropper, at two conservation conditions (5°C and 25°C), before and with simulated use. Analyses used were the following: visual inspection, cyclosporine quantification by a stability-indicating liquid chromatography method, osmolality and pH measurements and turbidity. A complementary analysis by dynamic light scattering was implemented to evaluate potential particle formation or micelle size change. In the in-use study, cyclosporine quantification was also performed on the drops emitted from the multidose eyedroppers. Our results show that the cyclosporine micellar formulation retains good physicochemical and microbiological stability, as all parameters stayed within acceptable range limits, however a higher variability in cyclosporine concentrations was observed for 20mg/mL units stored at 25°C. The in-use study showed that cyclosporine concentrations in the emitted drops were also within acceptable range limits. The micellar formulation presented in this study can therefore be stored at 5°C or at ≤25°C for up to 6months.

PCB contamination in fish community from the Gironde Estuary (France): blast from the past.

The contamination of the Gironde Estuary, southwest of France, by polychlorinated biphenyls (PCBs) was assessed using six fish of high ecological and economic importance as bioindicator species. The concentrations of 21 PCB congeners and total fat contents were determined in the muscle and liver of eels (Anguilla anguilla), seabass (Dicentrarchus labrax), flounders (Platichthys flesus), meagres (Argyrosomus regius), mullets (Liza ramada), and soles (Solea vulgaris). In addition, information regarding the trophic ecology of the studied fish was obtained through the analysis of carbon and nitrogen stable isotopes (i.e., δ(13)C and δ(15)N) in muscle. Results revealed high PCB concentrations in fish compared to monitored European estuaries. The muscle of eels was by far the most contaminated fish flesh (Σ7PCBs=1000±440 ng g(-1) on a dry weight basis), while the higher PCB concentrations in liver were measured in flounder (Σ7PCBs=2040±1160 ng g(-1) d.w.). A quantile regression approach allowed to investigate the fate of PCBs in the Gironde estuarine fish assemblage, and revealed a general process of trophic magnification. Finally, most of the analysed fish presented PCB concentrations in muscle meat above the current European maximum limits for sea products, while the derived "Toxic Equivalent Quantity" (TEQ) revealed human health concerns only for high-fat fish consumption.

In vitro evaluation of TiO2 nanotubes as cefuroxime carriers on orthopaedic implants for the prevention of periprosthetic joint infections.

CONTEXT: The prevention of periprosthetic joint infections requires an antibiotic prophylactic therapy, which could be delivered locally using titanium dioxide nanotubes as novel reservoirs created directly on the orthopaedic implant titanium surface. OBJECTIVE: In this study, the influence of several parameters that could impact the use of titanium dioxide nanotubes as cefuroxime carriers was investigated. METHOD: Cefuroxime loading and release was studied for 90 min with three nano-topography conditions (nano-smooth, nano-rugged and nano-tubular), two cefuroxime loading solution concentrations (150 mg/mL and 25mg/mL) and two nano-tubular crystalline structures. RESULTS: In all tested conditions, maximum amount of cefuroxime was obtained within 2 min. For both cefuroxime loading solution concentrations, nano-smooth samples released the least cefuroxime, and the nano-tubular samples released the most, and a six-fold increase in the concentration of the cefuroxime loading increased the amount of cefuroxime quantified by more than seven times, for all tested nano-topographies. However, the nano-tubes' crystalline structure did not have any influence on the amount of cefuroxime quantified. CONCLUSION: The results demonstrated that the surface nano-topography and loading solution concentration influence the efficiency of titanium dioxide nanotubes as cefuroxime carriers and need to be optimized for use as novel reservoirs for local delivery of cefuroxime to prevent periprosthetic infections.

Nanoporous surface wetting behavior: the line tension influence.

The aim of this work is to develop a physical model to describe the evolution of the apparent contact angle for four different liquids on nanotextured alumina surfaces with different pore radius. The nanoporous alumina templates were fabricated by anodization of Al foil in a 0.3 M oxalic acid solution. Scanning electron microscopy was used to characterize the morphology of the surfaces. The templates are approximately 400 nm in thickness and consist of a well-ordered hexagonal array of uniform radius pores spaced 105 nm apart with pore radii from 12 to 42 nm. The wettability of nanoporous alumina templates was investigated using contact-angle measurements. We measured the contact angles using four liquids: water, ethylene glycol, aniline, and a mixture of ethylene glycol and aniline. We developed a new theoretical model for the contact angle on nanoporous surfaces as a function of the pore radius. This model is based on energy considerations and involves liquid penetration into the nanopores driven by the capillarity (Laplace's law). Because the air is compressed inside the pores, this model also includes the effect of the line tension. This is important because the three-phase line length is greatly enhanced in our nanoporous structures. For example: for a millimeter-sized droplet, the three-phase line around the perimeter of the droplet is a few millimeters long, whereas the total three-phase line within the pores can reach several tens of meters. Using our model, the line-tension value for our nanopore samples is positive and ranges from 4 to 13 × 10(-9) N, which falls within the wide interval from 10(-11) to 10(-5) N quoted in the literature. Nanoporous surfaces may allow the effect of line tension to be visible for micro- to macrodroplets.

STEM and EDXS characterisation of physico-chemical reactions at the periphery of sol-gel derived Zn-substituted hydroxyapatites during interactions with biological fluids.

With its good properties of biocompatibility and bioactivity hydroxyapatite (HA) is highly used as bone substitutes and as coatings on metallic prostheses. In order to improve the bioactive properties of HA, we have elaborated Zn2+ doped hydroxyapatite. Zn2+ ions substitute for Ca2+ cations in the HA structure and four Zn concentrations (Zn/Zn+Ca) were prepared at 0.5, 1, 2 and 5 at.%. To study physico-chemical reactions at the materials periphery, we immersed the bioceramics into biological fluids for intervals from 1 day to 20 days. The surface changes were studied at the nanometer scale by scanning transmission electron microscopy associated with energy dispersive X-ray spectroscopy. After 20 days of immersion, we observed the formation of a calcium-phosphate layer at the periphery of the HA doped with 5% zinc. This layer contains magnesium and its thickness was around 200 nm. Formation of this Ca-P-Mg layer represents the bioactive properties of 5% Zn-substituted hydroxyapatite. This biologically active layer improves the properties of HA and will permit a chemical bond between the ceramic and bone.

Contamination by metallic elements released from joint prostheses.

When a metallic implant is in contact with human tissues, the organism reacts and a corrosion process starts. Consequently, we might observe liberation of metallic debris and wear. Our purpose is to measure the contamination and the migration of these metallic elements in the surrounding tissues of the implant. Two types of samples have been studied. First type is sample taken on post-mortem tissues around prostheses to study contamination gradients. Second type is sample taken on pathologic joints on periprosthetic capsular tissues in surgical conditions. These allow estimating contamination degree. The experiments were made on a Van de Graaff accelerator located at CERI (Centre d'Etude et de Recherche par Irradiation, Orléans, France). We measure elemental concentrations resulting from the contamination of the surface of each sample. Results are analysed in function of the pathology and the type of implants. According to the pathology and the location of the sampling, these measurements show a very heterogeneous contamination by metallic elements under particles and/or ionic species which can migrate through soft tissues by various mechanisms.