Elimination study of intact lipid nanocapsules after intravenous rat administration.

The present study investigated renal elimination after intravenous administration of four different formulations of lipid nanocapsules (LNCs) containing dyes adapted to Förster resonance energy transfer (FRET-LNCs). FRET-LNCs of 85 or 50 nm with or without a pegylated surface were injected and collected in the blood or urine of rats at different time points. Quantitative analysis was performed to measure intact FRET-LNCs.

[Exavir: Implementation and evaluation of experimental pharmacology skills acquisition by pharmacy students].

With the evolution of European and French regulations on animal experimentation in higher education, taking greater account of animal welfare, the University of Angers has developed a virtual animal experimentation software named Exavir. Used for practical work (PW) in physiology, pharmacology and toxicology in the Health, Sciences, and engineering curricula, Exavir can be used to simulate various experiments for teaching purposes, in vivo or ex vivo. Thanks to an original approach integrating serious games with different scenarios, students gain autonomy and become directly involved in their learning.

An experience of multidisciplinary tutorials sessions about antibiotics in the third year of pharmacy studies in Angers, France: learning assessment and evaluation of students' feelings by a mixed approach.

For undergraduate pharmacy students, the first step of antimicrobial stewardship learning objectives is to integrate antimicrobial knowledge from the foundational sciences. We hypothesised that using a multidisciplinary approach including two sessions of tutorials could be relevant in term of students' interest, satisfaction and learning retention time. The evaluation of students' feelings was based on a questionnaire including different dimensions and three focus groups with four students.

The dichotomous activities of microglia: A potential driver for phenotypic heterogeneity in Alzheimer's disease.

Alzheimer's disease (AD) is a leading cause of dementia, characterized by two defining neuropathological hallmarks: amyloid plaques composed of Aβ aggregates and neurofibrillary pathology. Recent research suggests that microglia have both beneficial and detrimental effects in the development of AD. A new theory proposes that microglia play a beneficial role in the early stages of the disease but become harmful in later stages.

Moving towards the implementation of pharmacogenetic testing in Quebec.

Clinical implementation of pharmacogenetics (PGx) into routine care will elevate the current paradigm of treatment decisions. However, while PGx tests are increasingly becoming reliable and affordable, several barriers have limited their widespread usage in Canada. Globally, over ninety successful PGx implementors can serve as models.

A revisited version of the disputatio for pharmacological training: An educational study.

Objective: The disputatio is a pedagogical method existing since the Middle-Ages where students had to debate about a question asked by a "master", exercising their thinking and oratory skills. To move away from traditional vertical teaching methods, the disputatio has been revived by pharmacologists. Thus, for almost three successive years, several groups of young French pharmacologists and therapists confronted their ideas concerning a medical question at a therapeutic impasse.

[An online tool to personalize the drug-doses for obese adults].

Background: Between 1975 and 2014, the number of people suffering from obesity tripled, reaching 17% of the adult population in France and more than 35% in the United States. Obesity is defined by a Body Mass Index (BMI)>30kg/m and characterized by a significant accumulation of adipose tissue responsible for the increase in weight. This accumulation leads to physiological changes capable of modifying the pharmacokinetics of drugs, which can lead to the administration of inappropriate doses.

Pharmacokinetics of obese adults: Not only an increase in weight.

Obesity is a pathophysiological state defined by a body mass index > 30 kg/m and characterized by an adipose tissue accumulation leading to an important weight increased. Several pathologies named comorbidities such as cardiovascular disease, type 2 diabetes and cancer make obesity the fifth cause of death in the world. Physiological changes impact the four main phases of pharmacokinetics of some drugs and leads to an inappropriate drug-dose.

Protein corona formation on lipidic nanocapsules: Influence of the interfacial PEG repartition.

The parameters currently used for characterization of nanoparticles, such as size and zeta potential, were not able to reflect the performance of a nanocarrier in the biological environment. Therefore, more thorough in vitro characterization is required to predict their behavior in vivo, where nanoparticles acquire a new biological identity due to interactions with biomolecules. In this present study, we performed in vitro characterization in biological fluids for lipid nanocapsules (LNCs) with varying means sizes (50 nm and 100 nm), different electrical surface charges and different Poly Ethylene Glycol (PEG) compositions.

Pharmacokinetics of intact lipid nanocapsules using new quantitative FRET technique.

The present study investigated the pharmacokinetics of intact lipid nanocapsules (LNCs) after intravenous administration in rats. Six different Förster resonance energy transfer LNCs (FRET-LNCs) have been studied with 2 sizes (50 and 85 nm) and 3 coating types (none, DSPE-mPEG 2000 or stearylamine). A FRET-LNCs blood extraction method was developed to retain an accurate FRET signal.

FRET as the tool for in vivo nanomedicine tracking.

Advanced drug delivery system utilizing a nanocarrier is the major application of nanotechnology on pharmacotherapeutics. However, despite the promising benefits and a leading trend in pharmaceutical research, nanomedicine development suffers from a poor clinical translation problem as only a handful of nanomedicine products reach the market yearly. The conventional pharmacokinetic study generally focuses only on monitoring the level of a free drug but ignores the nanocarrier's role in pharmacokinetics.

Tailoring PEGylated nanoparticle surface modulates inflammatory response in vascular endothelial cells.

Polymer nanoparticles (NPs) are extensively studied as drug delivery systems for various therapeutic indications, including drug and imaging agent delivery to the brain. Despite intensive research, their toxicological profile has yet to be fully characterized. In particular, the more subtle effects of nanomaterials on inflammatory processes have scarcely been investigated.

Organic nanoparticle tracking during pharmacokinetic studies.

To understand how nanoparticles (NPs) interact with biological barriers and to ensure they maintain their integrity over time, it is crucial to study their pharmacokinetic (PK) profiles. Many methods of tracking have been used to describe the fate of NPs and to evaluate their PKs and structural integrity. However, they do not deliver the same level of information and this may cause misinterpretations.

Teaching bacterial infections in pharmaceutical studies: why not 'with students' instead of 'to students'?

In pharmaceutical studies, a course of bacteriology based on case studies provided by the teacher was transformed in a course based on a combination of student/teacher co-creation of cases and peer reviewing. Our objectives were to describe the perception of students about the new format and to assess the impact of changing on the learning outcomes. For teaching evaluation, we used a questionnaire and focus groups.

New In Vitro Coculture Model for Evaluating Intestinal Absorption of Different Lipid Nanocapsules.

Standard models used for evaluating the absorption of nanoparticles like Caco-2 ignore the presence of vascular endothelium, which is a part of the intestinal multi-layered barrier structure. Therefore, a coculture between the Caco-2 epithelium and HMEC-1 (Human Microvascular Endothelial Cell type 1) on a Transwell insert has been developed. The model has been validated for (a) membrane morphology by transmission electron microscope (TEM); (b) ZO-1 and β-catenin expression by immunoassay; (c) membrane integrity by trans-epithelial electrical resistance (TEER) measurement; and (d) apparent permeability of drugs from different biopharmaceutical classification system (BCS) classes.

Specificity of pharmacokinetic modeling of nanomedicines.

Nanomedicines have been developed for more than four decades to optimize the pharmacokinetics (PK) of drugs, especially absorption, distribution, and stability in vivo. Unfortunately, only a few drug products have reached the market. One reason among others is the lack of proper PK modeling and evaluation, which impedes the optimization of these promising drug delivery systems.

Effects of physical activity on cell-to-cell communication during type 2 diabetes: A focus on miRNA signaling.

Type 2 diabetes (TD2) is a progressive disease characterized by hyperglycemia that results from alteration in insulin secretion, insulin resistance, or both. A number of alterations involving different tissues and organs have been reported to the development and the progression of T2D, and more relevantly, through cell-to-cell communication pathways. Recent studies demonstrated that miRNAs are considerably implicated to cell-to-cell communication during T2D.

Novel hybrid lipid nanocapsules loaded with a therapeutic monoclonal antibody - Bevacizumab - and Triamcinolone acetonide for combined therapy in neovascular ocular pathologies.

The aim of this study was to design and develop a novel hybrid formulation based on lipid nanocapsules containing bevacizumab (BVZ), an effective therapeutic antibody, on the surface and triamcinolone acetonide (TA) in the inner core (BVZ-TA-LNC) intended to improve ocular therapy. Hence, a phase inversion-insertion one step method was developed to drug loading and surface modification of lipid nanocapsules by post-insertion of a bifunctional polymer, followed by antibody coupling using "click" chemistry. The covalent bond and antibody capacity binding to its specific antigen were confirmed by thermal analysis and immunoassay, respectively.

Selective deficiency in endothelial PTP1B protects from diabetes and endoplasmic reticulum stress-associated endothelial dysfunction via preventing endothelial cell apoptosis.

Diabetes notably increases the risk for endothelial dysfunction, a main precursor for microvascular complications. While endoplasmic reticulum stress (ERS) and protein tyrosine phosphatase 1B (PTP1B) have been associated with endothelial dysfunction in resistance vessels, whether these mechanisms also contribute to diabetes-mediated endothelial dysfunction in conduit arteries remains unknown. Herein, we tested the hypothesis that diabetes induces macrovascular endothelial dysfunction via endothelial ERS-induced, PTP1B-mediated apoptosis.

Novel Insights into the Mode of Action of Vasorelaxant Synthetic Polyoxygenated Chalcones.

Polyphenols consumption has been associated with a lower risk of cardiovascular diseases (CVDs) notably through nitric oxide (NO)- and estrogen receptor α (ERα)-dependent pathways. Among polyphenolic compounds, chalcones have been suggested to prevent endothelial dysfunction and hypertension. However, the involvement of both the NO and the ERα pathways for the beneficial vascular effects of chalcones has never been demonstrated.

Di--lauroyl-decitabine-lipid nanocapsules: toward extending decitabine activity.

Background: Acute myeloid leukemia mainly affects adult patients. Complete remission for patients younger than 60 years, who are candidates for standard induction therapy, is achieved in 60%-80% of cases. However, the prognosis is still poor for older patients, who are unfit for intensive chemotherapy, and only a few therapies are available.

Design, Synthesis, Pharmacological Evaluation and Vascular Effects of Delphinidin Analogues.

Background: Among polyphenolic compounds suggested to prevent cardiovascular diseases (CVDs) and to explain the "French paradox", the anthocyanidin delphinidin (Dp) has been reported to support at least partly the vascular beneficial effects of dietary polyphenolic compounds including those from fruits and related products as red wine. It has also been highlighted that Dp interacts directly with the active site of estrogen receptor α (ERα), leading to activation of endothelial NO synthase (eNOS) pathway thus contributing to the prevention of endothelial dysfunction in mice aorta. However, anthocyanidins have very low bioavailability and despite a well described in vitro efficacy, the very high hydrophilicity and physicochemical instability of Dp might explain the lack of in vivo reported effects.

In vivo comparison of the proangiogenic properties of chlordecone and three of its dechlorinated derivatives formed by in situ chemical reduction.

In situ chemical reduction (ISCR) has been identified as a possible way for the remediation of soils contaminated by chlordecone (CLD). Evidences provided by the literature indicate an association between the development of prostate cancer and CLD exposure (Multigner et al. 2010).

Unusual modes of action of the repellent DEET in insects highlight some human side effects.

N,N-diethyl-m-toluamide (DEET) induces favorable repellency against insects by acting on the sensory nervous system. According to emerging literature reports, DEET side effects in humans involve new molecular targets including the cholinergic system, acetylcholinesterase (AChE), muscarinic M1 and M3 receptor and the participation of the second messenger nitric oxide (NO). Most of these molecular events targeted by DEET have previously been characterized in insects while they have been considered as marginal compared to classical repellent properties.

Is bisphenol A an environmental obesogen?

Bisphenol A (BPA) is an endocrine disruptor with an oestrogenic activity that is widely produced for the manufacture of polycarbonate plastic, epoxy resin, and thermal paper. Its ubiquitous presence in the environment contributes to broad and continuous human exposure, which has been associated with deleterious health effects. Despite numerous controversial discussions and a lack of consensus about BPA's safety, growing evidence indicates that BPA exposure positively correlates with an increased risk of developing obesity.