Direct nose-to-brain delivery has been raised as a non-invasive powerful strategy to deliver drugs to the brain bypassing the blood-brain barrier (BBB). This study aimed at preparing and characterizing an innovative composite formulation, associating the liposome and hydrogel approaches, suitable for intranasal administration. Thermosensitive gel formulations were obtained based on a mixture of two hydrophilic polymers (Poloxamer 407, P407 and Poloxamer 188, P188) for a controlled delivery through nasal route via liposomes of an active pharmaceutical ingredient (API) of potential interest for Alzheimer’s disease. The osmolarity and the gelation temperature (T° sol-gel) of formulations, defined in a ternary diagram, were investigated by rheometry and visual determination. Regarding the issue of assays, a mixture composed of P407/P188 (15/1%, w/w) was selected for intranasal administration in terms of T° sol-gel and for the compatibility with the olfactory mucosal (280 ± 20 mOsmol, pH 6). Liposomes of API were prepared by the thin film hydration method. Mucoadhesion studies were performed by using mucin disc, and they showed the good natural mucoadhesive characteristics of in situ gel formulations, which increased when liposomes were added. The study demonstrated successful pharmacotechnical development of a promising API-loaded liposomes in a thermosensitive hydrogel intended for nasal Alzheimer’s disease treatment.

Since 1998, the French Health Insurance (NHI) system had established a national database in order to reimburse drug prescriptions. These electronical data are a considerable potential source for syndromic surveillance because of their exhaustive and regular updates. The aim of this study was to develop a method to identify acute gastroenteritis (AG) cases from drug reimbursements of the NHI database. The algorithm aimed at discriminating AG from other pathologies was determined from a sample of 206 AG prescriptions and 351 non-AG prescriptions collected in five pharmacies. The AG case identification was mainly based on the lag time between the prescription and delivery day, the occurrence of non-AG case-specific drugs, AG case-specific drug associations and treatment duration. The discriminant algorithm led to a sensitive and specific indicator of medically treated cases of AG with a time–spatial resolution power which met the need for waterborne AG surveillance.

The study addresses the hypothesis that endothelial dysfunction in experimental arterial hypertension can be related to an alteration in epoxyeicosatrienoic acids (EETs) pathway and can be prevented by the inhibition of EETs degradation by soluble epoxide hydrolase (sEH). Arterial hypertension was induced in FVB/N mice by renal artery stenosis ('two-kidney-one-clip', 2K1C). Seven weeks after surgery, increased aortic pressures (Millar tonometer; Millar Instruments, Houston, Texas, USA) and cardiac hypertrophy (echocardiography) were present in 2K1C mice as compared with control mice. Left coronary artery endothelium-dependent relaxations to acetylcholine were decreased in 2K1C mice without modification in the relaxing responses to NS309 and NS1619, the openers of calcium-activated potassium channels mediating the hyperpolarizing effect of EETs. The inhibitors of the EET-synthesizing enzymes cytochrome P450 epoxygenases, fluconazole and N-methylsulfonyl-6-(2-propargyloxyphenyl)-hexanamide (MSPPOH), reduced the coronary relaxations to acetylcholine in control but not in 2K1C mice. The sEH expression was increased in 2K1C mice. The sEH inhibitor 12-(3-adamantan-1-yl-ureido)dodecanoic acid administered for 2 weeks starting 5 weeks after surgery in 2K1C mice (25 mg/l in drinking water) reduced aortic pressures and cardiac hypertrophy, improved the coronary relaxations to acetylcholine and restored the inhibitory effect of fluconazole and MSPPOH on acetylcholine-induced relaxations, without modifying the relaxations to NS309 and NS1619. These results demonstrate that a reduced EET-mediated relaxations related to an increased degradation by sEH contributes to coronary endothelial dysfunction in 2K1C hypertensive mice. Inhibiting sEH prevents endothelial dysfunction by restoring EET-mediated relaxations and thus, could represent a promising pharmacological intervention to limit cardiovascular morbidity and mortality in arterial hypertension.

We present herein the preparation of novel polymer inclusion membranes (PIMs) containing insoluble β-CD polymer as a carrier, polyvinyl chloride as a base polymer, and dibuthylphtalate (DBP) as a plasticizer in varying proportions. The prepared PIMs can be obtained by a simple, fast, and high-yield preparation process. Physicochemical characterizations of such membranes occurred in a homogeneous structure. In addition, Fourier-transform infrared Spectroscopy (FT-IR) analysis found that DBP was inserted between these polymeric chains by non-covalent interactions. This led to a spacing of PVC/poly(β-cyclodextrin) chains inducing a better access of guest molecules to PIM cyclodextrins. To achieve the elimination of ibuprofen and progesterone, two examples of emerging environmental contaminants that can lead to possible alterations to aquatic environments and affect human health, the effect of three operating parameters was studied (pH, the proportion of β-cyclodextrin polymer, and wastewater agitation). The proportion of β-cyclodextrin polymer and wastewater agitation had a favorable influence on drug extraction at 10 ppm. The PIMs containing β-cyclodextrin polymer was unstable in basic conditions and was more effective at acidic pH. These initial results demonstrate the high potential for drug extraction of this polymer.