2023

Un article intitulé "  Unravelling the Role of Uncommon Hydrogen Bonds in Cyclodextrin Ferrociphenol Supramolecular Complexes: A Computational Modelling and Experimental Study " vient de paraître dans " International Journal of Molecumlar Science "

Auteurs :  Pigeon P, Najlaoui F, McGlinchey M J, García J S, Jaouen G, Gibaud S

Int. J. Mol. Sci. 2023, 24(15), 12288; https://doi.org/10.3390/ijms241512288

 

Abstract

We sought to determine the cyclodextrins (CDs) best suited to solubilize a patented succinimido-ferrocidiphenol (SuccFerr), a compound from the ferrociphenol family having powerful anticancer activity but low water solubility. Phase solubility experiments and computational modelling were carried out on various CDs. For the latter, several CD-SuccFerr complexes were built starting from combinations of one or two CD(s) where the methylation of CD oxygen atoms was systematically changed to end up with a database of ca. 13 k models. Modelling and phase solubility experiments seem to indicate the predominance of supramolecular assemblies of SuccFerr with two CDs and the superiority of randomly methylated β-cyclodextrins (RAMEβCDs). In addition, modelling shows that there are several competing combinations of inserted moieties of SuccFerr. Furthermore, the models show that ferrocene can contribute to high stabilization by making atypical hydrogen bonds between Fe and the hydroxyl groups of CDs (single bond with one OH or clamp with two OH of the same glucose unit).

Un article intitulé " The AT1/AT2 Receptor Equilibrium Is a Cornerstone of the Regulation of the Renin Angiotensin System beyond the Cardiovascular System " vient de paraître dans " Molecules "

Auteurs : Colin M, Delaitre C, Foulquier S, Dupuis F

Molecules 2023, 28(14), 5481; https://doi.org/10.3390/molecules28145481

 

Abstract

The AT1 receptor has mainly been associated with the pathological effects of the renin-angiotensin system (RAS) (e.g., hypertension, heart and kidney diseases), and constitutes a major therapeutic target. In contrast, the AT2 receptor is presented as the protective arm of this RAS, and its targeting via specific agonists is mainly used to counteract the effects of the AT1 receptor. The discovery of a local RAS has highlighted the importance of the balance between AT1/AT2 receptors at the tissue level. Disruption of this balance is suggested to be detrimental. The fine tuning of this balance is not limited to the regulation of the level of expression of these two receptors. Other mechanisms still largely unexplored, such as S-nitrosation of the AT1 receptor, homo- and heterodimerization, and the use of AT1 receptor-biased agonists, may significantly contribute to and/or interfere with the settings of this AT1/AT2 equilibrium. This review will detail, through several examples (the brain, wound healing, and the cellular cycle), the importance of the functional balance between AT1 and AT2 receptors, and how new molecular pharmacological approaches may act on its regulation to open up new therapeutic perspectives

 

Un article intitulé " Modulation of release and pharmacokinetics from nanoscale lipid prodrugs of dexamethasone with variable linkage chemistry " vient de paraître dans " Journal of Controlled Release "

Auteurs : Ur-Rehman M, Reynaud F, Lepetre S, Abreu S, Chaminade P, Fattal E, Tsapis N

Journal of Controlled Release , Volume 360, August 2023, Pages 293-303 , https://doi.org/10.1016/j.jconrel.2023.06.031

 

Abstract

 

In an attempt to tune drug release and subsequent pharmacokinetics once administered intravenously, we have synthesized three lipid-drug conjugates (LDCs) of dexamethasone (DXM) each possessing a different lipid-drug chemical linkage: namely ester, carbamate and carbonate. These LDCs were thoroughly characterized before being turned into nanoscale particles by an emulsion-evaporation process using DSPE-PEG2000 (Distearoyl-sn-Glycero-3-Phosphoethanolamine-N-(methoxy(polyethylene glycol)-2000) as the only excipient. Spherical nanoparticles (NPs) of about 140–170 nm, with a negative zeta potential, were obtained for each LDC and exhibited good stability upon storage at 4 °C for 45 days with no recrystallization of LDCs observed. LDC encapsulation efficacy was above 95% for the three LDCs, leading to a LDC loading of about 90% and an equivalent DXM loading above 50%. Although the ester and carbonate NPs did not exhibit any toxicity up to an equivalent DXM concentration of 100 μg/mL, the carbamate LDC NPs appeared very toxic towards RAW 264.7 macrophages and were discarded. Both ester and carbonate LDC NPs were shown to exert anti-inflammatory activity on LPS-activated macrophages. DXM release from LDC NPs in murine plasma was faster from ester than from carbonate NPs. Finally, pharmacokinetics and biodistribution were conducted, showing a lower exposure to DXM from carbonate LDC NPs than from ester LDC NPs, correlated with the slower DXM release from carbonate LDC NPs. These results outline the need for extended studies to find the best prodrug system for extended drug release.

Nous sommes heureux d’annoncer la nomination à l’Institut Universitaire de France comme membre Junior en chaire innovation de Ariane Boudier.

C’est une excellente nouvelle !

Un article intitulé " Activity and reusability of immobilized gold nanoparticles for the catalysis of both oxidation and reduction reactions " vient de paraître dans "Results in Chemistry"

Auteurs : Boukoufi C, Boudier A, Lahouari S, Vigneron J, Clarot I

Results in Chemistry, in press, Journal pre-proof, 100979, https://doi.org/10.1016/j.rechem.2023.100979

 

 

Abstract

 

Colloidal gold nanoparticles (AuNP) are well-known to present a catalytic activity. However, they are characterized by certain limitations, as a rather poor stability and lack of both handling and reusability. Their immobilization on surfaces could help to overcome these drawbacks. This work evaluated the impact of the immobilization of AuNP towards their catalytic activity on reduction and oxidation reactions. Colloidal AuNP stabilized with citrate ions were synthesized, characterized, and immobilized by the dip-coating method, the obtained immobilized AuNP (iAuNP) were characterized. The catalytic activity of AuNP and iAuNP was evaluated and compared to each other through the p-nitrophenol reduction reaction. The kinetic of the catalytic activity of iAuNP was slower than colloidal AuNP. The catalytic activity appeared to be impacted by the less available surface of iAuNP. The reduction efficiency of iAuNP was also evaluated with the DPPH•/DPPH2 reduction reaction. The capacity of iAuNP to catalyze the reduction of DPPH• in DPPH2 was shown even after 130 days and 20 reuses of the nanostructured surface on the contrary to non-reusable colloidal AuNP. The oxidation efficiency of iAuNP was measured by the ability to catalyze the auto-oxidation of curcumin (HPLC-UV/vis). For all these experiments, the addition of 4-mercapto-phenol on the surface of iAuNP passivated the surface, decreasing the catalytic activity of the materials. In conclusion, iAuNP are redox catalysts with both anti- and pro-oxidant effects and high reusability over a very long period.

Un article intitulé "Cross-frontal mode: An alternative methodology for Taylor dispersion analysis of monomodal sample" vient de paraître dans "Journal of Chromatography A".

Auteurs : Gouyon J, Boudier A, Pallotta A, Boukoufi C, Clarot I

Journal of Chromatography A, Volume 1694, 2023, 463913.https://doi.org/10.1016/j.chroma.2023.463913

 

Abstract

 

Taylor dispersion analysis (TDA) is a technique dedicated to the determination of the molecular diffusion coefficient (D) of species, using band broadening of an analyte in a laminar flow. Two modes are commonly used to perform TDA: pulse and frontal modes. In each case, a fitting of the signal is required. We propose here a third mode denoted as cross-frontal mode, combining two crossed sample fronts without modification of a classical CE device for the rapid and accurate determination of D of caffeine, reduced glutathione (GSH), insulin from bovine pancreas, bovine serum albumin (BSA) and citrate-capped gold nanoparticles (AuNP). Theoretical aspects and methodology are described, showing a good correlation between the so-called cross-frontal mode and usual frontal mode. Limitations of the techniques are also assessed, and are similar to regular modes while no fitting is required. This new methodology allows improving the sensitivity toward low concentrated sample compared to pulse mode, and an alternative mathematical treatment compared to regular TDA modes.

 

2022

Un article intitulé " Metal-chelating activity of soy and pea protein hydrolysates obtained after different enzymatic treatments from protein isolates " vient de paraître dans " Food Chemistry "

Auteurs : Sarah El Hajj, Rachel Irankunda, Jairo Andrés Camaño Echavarría, Philippe Arnoux, Cédric Paris, Loic Stefan, Caroline Gaucher, Sandrine Boschi-Muller, Laetitia Canabady-Rochelle

Food Chemistry, Volume 405, Part A, 134788. https://doi.org/10.1016/j.foodchem.2022.134788

 

Abstract

 

Soy and pea proteins are two rich sources of essential amino acids. The hydrolysis of these proteins reveals functional and bioactive properties of the produced small peptide mixtures. In our study, we employed the hydrolysis of soy and pea protein isolates with the endopeptidases Alcalase® and Protamex®, used alone or followed by the exopeptidase Flavourzyme®. The sequential enzyme treatments were the most efficient regarding the degree of hydrolysis. Then, soy and pea protein hydrolysates (SPHs and PPHs, respectively) were ultrafiltrated in order to select peptides of molecular weight ≤ 1 kDa. Whatever the protein source or the hydrolysis treatment, the hydrolysates showed similar molecular weight distributions and amino acid compositions. In addition, all the ultrafiltrated hydrolysates possess metal-chelating activities, as determined by UV-spectrophotometry and Surface Plasmon Resonance (SPR). However, the SPR data revealed better chelating affinities in SPHs and PPHs when produced by sequential enzymatic treatment.

Un article intitulé " Taylor dispersion analysis of metallic-based nanoparticles – A short review " vient de paraître dans " Electrophoresis "

Auteurs : Jeremie Gouyon, Ariane Boudier, Fatima Barakat, Arnaud Pallotta, Igor Clarot

Electrophoresis, 2022, https://doi.org/10.1002/elps.202200184

 

Abstract

 

Taylor dispersion analysis (TDA) is an interesting tool for nanoparticle (NP) size determination, feasible using simple capillary electrophoresis apparatus. Based upon the radial diffusion of analytes upon a laminar stream, the diffusion coefficient of species is easily estimable. Moreover, TDA is generally more adequate than conventional dynamic light scattering methodologies as it is less dependent on the polydispersity of the sample, leading to accurate measurement and reliable results. This review provides every paper mentioning the use of TDA for metallic-based NPs size determination. Diverse strategies for the detection of metallic NPs (like UV–visible and inductively coupled plasma–mass spectrometry – ICP–MS – for instance) and interpretation of the Taylorgrams are discussed. Based upon the literature, advices on future prospects are also indicated, especially for the comparison of TDA results with other classical techniques.

Un article intitulé " Thiol sensing: From current methods to nanoscale contribution " vient de paraître dans " Microchemical Journal "

Auteurs : Margaux Berthou, Igor Clarot, Jeremie Gouyon, Damien Steyer, Marie Anais Monat, Ariane Boudier, Arnaud Pallotta

Microchemical Journal, 183, 2022, 107994. https://doi.org/10.1016/j.microc.2022.107994

Abstract

Thiols play critical roles in many biologicals processes: they are involved in combating oxidative stress and maintaining redox homeostasis. In agri-food, they are responsible for organoleptic aspect of many foodstuffs. Thus, thiol identification and quantification are challenging due to their similar chemical structures (especially for small/volatile thiols), reactivity and matrices of these compounds. To overcome the analytical issues, many methods and technics were developed each with their own advantages and drawbacks. Lately, one emerging field in analytical development goes through the contribution of nanoparticles. Scientific teams rely on their unique properties to improve sensitivity, selectivity and decrease matrices effects. This review is an overview of current methods for thiol detection followed by the report of nanomaterial contribution to the field. Finally, a critical point of view will be given to these new sensing methods, from their potential to their limits.

Margaux BERTHOU soutiendra sa thèse de doctorat intitulée "Monitoring de thiols et S-nitrosothiols à l'aide d'un dispositif nanostructuré" le mardi 20 septembre à 9h dans l'amphithéatre Lepois du campus Brabois santé.

Le jury est composé de :

- Mme Catherine FOULON (Rapporteur, Pr, EA 7365, Université de Lille, Lille)

- Mme Murielle ROCHELET (Rapporteur, Dr, AgroSup, Université de Bourgogne)

- Mme Corine RAVELET (Examinateur, Pr, UMR 5063, Université de Genoble-Rhone-Alpes, Grenoble)

- M. Emmanuel LAMOUROUX (Examinateur, Dr, UMR 7565 Université de Lorraine, Nancy)

- M. Igor CLAROT (Examinateur, PR, EA 3452 CITHEFOR Université de Lorraine, Nancy, Directeur de thèse)

- M. Arnaud PALLOTTA (Examinateur, Dr, EA 3452 CITHEFOR Université de Lorraine, Nancy, Co-directeur de thèse)