Interest of flow injection spectrophotometry as an orthogonal method for analyzing biomolecule aggregates: Application to stressed monoclonal antibody study.

This study aimed to explore the suitability of flow injection spectrophotometry (FIS) to analyze three degraded therapeutic monoclonal antibodies (bevacizumab, nivolumab, and rituximab). For this purpose, aggregates were generated with stirring, freeze-thaw, and heat stresses. The intact and stressed mab samples were filtered with 0.

Hemocompatibility and safety of the Carmat Total Artifical Heart hybrid membrane.

The Carmat bioprosthetic total artificial heart (C-TAH) is a biventricular pump developed to minimize drawbacks of current mechanical assist devices and improve quality of life during support. This study aims to evaluate the safety of the hybrid membrane, which plays a pivotal role in this artificial heart. We investigated in particular its blood-contacting surface layer of bovine pericardial tissue, in terms of mechanical aging, risks of calcification, and impact of the hemodynamics shear stress inside the ventricles on blood components.

"Microchip Electrophoresis," with Respect to "Profiling of Aβ Peptides in the Cerebrospinal Fluid of Patients with Alzheimer's Disease".

Aggregation of beta-amyloid peptides especially Aβ1-42 in amyloid plaques is one of the major neuropathological events in Alzheimer's disease. This event is normally accompanied by a relative reduction of the concentration of Aβ1-42 in the cerebrospinal fluid (CSF) of patient developing the signs of Alzheimer's disease. Here, we describe methods for isolation and for microchip gel electrophoresis of Aβ peptides in polydimethylsiloxane (PDMS) microfluidic chip.

UV spectroscopy and least square matching for high throughput discrimination of taxanes in commercial formulations and compounded bags.

The need for high-throughput quality control of pharmaceuticals after compounding is often required before the treatment of the patients. Ultra-fast analysis using flow injection analysis coupled to UV spectroscopy and least square matching was assessed for the simultaneous quantification and identification of three therapeutic taxanes after dilution in physiological saline (cabazitaxel, docetaxel, and paclitaxel). In-depth preliminary analysis of the zero and first order UV spectra of the taxanes using principal component analysis (PCA) allowed us focusing on relevant spectral range with very low formulation influence.

Intestinal permeability determinants of norfloxacin in Ussing chamber model.

Recently, many efforts are taken to identify the intestinal uptake and efflux transporters since they are responsible for the absorption of many drugs as their interactions. Norfloxacin (NFX) is a fluoroquinolone that presents low solubility and low permeability, and as a consequence, low bioavailability. In this context, the aim of this study is evaluate for the first time the intestinal permeability mechanisms of NFX by Ussing chamber model.

Simple and ultra-fast recognition and quantitation of compounded monoclonal antibodies: Application to flow injection analysis combined to UV spectroscopy and matching method.

Compounding of monoclonal antibody (mAbs) constantly increases in hospital. Quality control (QC) of the compounded mAbs based on quantification and identification is required to prevent potential errors and fast method is needed to manage outpatient chemotherapy administration. A simple and ultra-fast (less than 30 s) method using flow injection analysis associated to least square matching method issued from the analyzer software was performed and evaluated for the routine hospital QC of three compounded mAbs: bevacizumab, infliximab and rituximab.

Optimization of classification and regression analysis of four monoclonal antibodies from Raman spectra using collaborative machine learning approach.

The use of monoclonal antibodies (mAbs) constitutes one of the most important strategies to treat patients suffering from cancers such as hematological malignancies and solid tumors. These antibodies are prescribed by the physician and prepared by hospital pharmacists. An analytical control enables the quality of the preparations to be ensured.

[Synthesis and binding affinity to human steroid hormone receptors of 3-phenoxy-4-hydroxycoumarins and 3-phenoxy-4-phenylcoumarins].

The synthesis and the study of the binding affinity to human receptors of glucocorticoids, mineralcorticoids, androgens, estrogens and progesterone of 3-phenoxy-4-hydroxycoumarins and 3-phenoxy-4-phenylcoumarins were performed. It shows the absence of any binding affinity of all these derivatives to glucocorticoid and mineralcorticoid receptors and a non-selective binding affinity to androgen, oestrogen and progesterone receptors with 3-phenoxy-4-phényl-coumarins.

Clinical screening of paraquat in plasma samples using capillary electrophoresis with contactless conductivity detection: Towards rapid diagnosis and therapeutic treatment of acute paraquat poisoning in Vietnam.

The employment of a purpose-made capillary electrophoresis (CE) instrument with capacitively coupled contactless conductivity detection (CD) as a simple and cost-effective solution for clinical screening of paraquat in plasma samples for early-stage diagnosis of acute herbicide poisoning is reported. Paraquat was determined using an electrolyte composed of 10mM histidine adjusted to pH 4 with acetic acid. A detection limit of 0.

Rapid discrimination and determination of antibiotics drugs in plastic syringes using near infrared spectroscopy with chemometric analysis: Application to amoxicillin and penicillin.

The aim of this study was to investigate near infrared spectroscopy (NIRS) combined to chemometric analysis to discriminate and quantify three antibiotics by direct measurement in plastic syringes.Solutions of benzylpenicillin (PENI), amoxicillin (AMOX) and amoxicillin/clavulanic acid (AMOX/CLAV) were analyzed at therapeutic concentrations in glass vials and plastic syringes with NIR spectrometer by direct measurement. Chemometric analysis using partial least squares regression and discriminative analysis was conducted to develop qualitative and quantitative calibration models.

Novel Water-Soluble Mucoadhesive Carbosilane Dendrimers for Ocular Administration.

The purpose of this research was to determine the potential use of water-soluble anionic and cationic carbosilane dendrimers (generations 1-3) as mucoadhesive polymers in eyedrop formulations. Cationic carbosilane dendrimers decorated with ammonium -NH3(+) groups were prepared by hydrosylilation of Boc-protected allylamine and followed by deprotection with HCl. Anionic carbosilane dendrimers with terminal carboxylate groups were also employed in this study.

Validation of a preclinical model for assessment of drug efficacy in melanoma.

The aim of personalized medicine is to improve our understanding of the disease at molecular level and to optimize therapeutic management. In this context, we have developed in vivo and ex vivo preclinical strategies evaluating the efficacy of innovative drugs in melanomas. Human melanomas (n = 17) of different genotypes (mutated BRAF, NRAS, amplified cKIT and wild type) were successfully engrafted in mice then amplified by successive transplantations.

The probiotic Propionibacterium freudenreichii as a new adjuvant for TRAIL-based therapy in colorectal cancer.

TNF-Related Apoptosis-Inducing Ligand (TRAIL) is a well-known apoptosis inducer, which activates the extrinsic death pathway. TRAIL is pro-apoptotic on colon cancer cells, while not cytotoxic towards normal healthy cells. However, its clinical use is limited by cell resistance to cell death which occurs in approximately 50% of cancer cells.

In vitro and in vivo antileishmanial properties of a 2-n-propylquinoline hydroxypropyl β-cyclodextrin formulation and pharmacokinetics via intravenous route.

2-n-propylquinoline (2-n-PQ) had shown interesting in vivo antileishmanial activities after administration by oral route on leishmaniasis animal models. However, the lipophilic properties of this compound avoid its use by intravenous route, this route being indicated in cases of severe visceral leishmaniasis with vomiting. Thus, a 2-n-propylquinoline hydroxypropyl beta-cyclodextrin (2-n-PQ-HPC) formulation was set up in this aim.

Ex vivo permeation of tamoxifen and its 4-OH metabolite through rat intestine from lecithin/chitosan nanoparticles.

Tamoxifen citrate is an anticancer drug slightly soluble in water. Administered orally, it shows great intra- and inter-patient variations in bioavailability. We developed a nanoformulation based on phospholipid and chitosan able to efficiently load tamoxifen and showing an enzyme triggered release.

Design, characterisation, and bioefficiency of insulin-chitosan nanoparticles after stabilisation by freeze-drying or cross-linking.

Insulin delivery by oral route would be ideal, but has no effect, due to the harsh conditions of the gastrointestinal tract. Protection of insulin using encapsulation in self-assembled particles is a promising approach. However, the lack of stability of this kind of particles in biological environments induces a low bioavailability of encapsulated insulin after oral administration.

First enantioselective total synthesis and configurational assignments of suberosenone and suberosanone as potential antitumor agents.

The first enantioselective total syntheses of two marine sesquiterpenes (1R)-suberosenone and (1R)-suberosanone are achieved leading to revision of the AC of natural (1S)-suberosanone. Key elements of the synthesis include hyperbaric asymmetric Michael addition and highly efficient silver trifluoroacetate mediated α-alkylation for the formation of ring A.

Neutral polymers as coatings for high resolution electrophoretic separation of Aβ peptides on glass microchips.

This study reports a comparison of the performances of two neutral polymers, poly ethylene-oxide (PEO) and poly(dimethylacrylamide-co-allyl glycidyl ether) (EpDMA), in glass microchips to achieve zone electrophoresis separation of several truncated forms of beta amyloid (Aβ) peptides, sharing very similar structures. The peptides were derivatized by FluoProbes 488 NHS to allow their fluorescence detection. Two protocols based either on PEO or EpDMA led to good pH stabilities in addition to a significant reduction of the electroosmotic flow.

Structure-activity relationships of sugar-based peptidomimetics as modulators of amyloid β-peptide early oligomerization and fibrillization.

Alzheimer's disease is a neurodegenerative disorder linked to oligomerization and fibrillization of amyloid β peptides. Aβ1-42 being the most aggregative and neurotoxic amyloid peptide, we report herein the capacity of sugar-based pentapeptide analogs to modulate the Aβ1-42 aggregation process using thioflavin fluorescence and transmission electron microscopy assays. The importance of the free hydroxyl groups of the sugar moiety, used as a β-breaker element, is confirmed since hydroxylated compounds inhibit the aggregation process while benzylated ones enhance it.

An improved capillary electrophoresis method for in vitro monitoring of the challenging early steps of Aβ1-42 peptide oligomerization: application to anti-Alzheimer's drug discovery.

We report an improved CE method to monitor in vitro the self-assembly of monomeric amyloid β-peptide (42 amino acids amyloid β-peptide, Aβ1-42 ) and in particular the crucial early steps involved in the formation of the neurotoxic oligomers. In order to start the kinetics from the beginning, sample preparation was optimized to provide samples containing exclusively the monomeric form. The CE method was also improved using a dynamic coating and by reducing the separation distance.

VDAC phosphorylation, a lipid sensor influencing the cell fate.

The voltage-dependent anion channel (VDAC) or porin is a major membrane protein integrated into the mitochondrial outer membrane in eukaryotes. It is encoded as three isoforms (VDAC1 to 3), which play differential roles in metabolism and cell death. As a channel, VDAC mediates metabolites, ions and water movements through the outer membrane in physiological conditions, but it can also participate to mitochondrial membrane permeabilization, an apoptotic checkpoint in stress and pathological conditions.

Development of antileishmanial lipid nanocomplexes.

Visceral leishmaniasis is a life-threatening disease that affects nearly a million people every year. The emergence of Leishmania strains resistant to existing drugs complicates its treatment. The purpose of this study was to develop a new lipid formulation based on nanocochleates combining two active drugs: Amphotericin B (AmB) and Miltefosine (HePC).

Systems biology of cisplatin resistance: past, present and future.

The platinum derivative cis-diamminedichloroplatinum(II), best known as cisplatin, is currently employed for the clinical management of patients affected by testicular, ovarian, head and neck, colorectal, bladder and lung cancers. For a long time, the antineoplastic effects of cisplatin have been fully ascribed to its ability to generate unrepairable DNA lesions, hence inducing either a permanent proliferative arrest known as cellular senescence or the mitochondrial pathway of apoptosis. Accumulating evidence now suggests that the cytostatic and cytotoxic activity of cisplatin involves both a nuclear and a cytoplasmic component.