Actualités

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)

Nous accueillons au sein de l'équipe de nouveaux arrivants :

- Franceline Reynaud, Maitre de Conférences en Pharmacie galénique

- Gladys Bantsimba Malanda, ATER en Pharmacologie

- Diego Ramos, ATER en Pharmacie Galénique

Bienvenue à eux trois !

Un article intitulé " Succinimido–Ferrocidiphenol Complexed with Cyclodextrins Inhibits Glioblastoma Tumor Growth In Vitro and In Vivo without Noticeable Adverse Toxicity " vient de paraître dans " Molecules "

Auteurs : Feten Najlaoui, Benoit Busser, Germain Sotoing Taïwe, Pascal Pigeon, Nathalie Sturm, Diane Giovannini, Naziha Marrakchi, Ali Rhouma, Gérard Jaouen, Stéphane Gibaud et Michel De Waard

Molecules 2022, 27(14), 4651; https://doi.org/10.3390/molecules27144651

Abstract

SuccFerr(N-[4-ferrocenyl,5-5-bis(4-hydroxyphenyl)-pent-4-enyl]-succinimide) has remarkable antiproliferative effects in vitro, attributed to the formation of a stabilized quinone methide. The present article reports in vivo results for a possible preclinical study. SuccFerr is lipophilic and insoluble in water, so the development of a formulation to obviate this inconvenience was necessary. This was achieved by complexation with randomly methylated cyclodextrins (RAMEßCDs). This supramolecular water-soluble system allowed the in vivo experiments below to proceed. Application of SuccFerr on the glioblastoma cancer cell line U87 indicates that it affects the cellular cycle by inducing a blockade at G0/G1 phase, linked to apoptosis, and another one at the S phase, associated with senescence. Using healthy Fischer rats, we show that both intravenous and subcutaneous SuccFerr: RAMEßCD administration at 5 mg/kg lacks toxic effects on several organs. To reach lethality, doses higher than 200 mg/kg need to be administered. These results prompted us to perform an ectopic in vivo study at 1 mg/kg i.v. ferrocidiphenol SuccFerr using F98 cells xenografted in rats. Halting of cancer progression was observed after six days of injection, associated with an immunological defense response linked to the active principle. These results demonstrate that the properties of the selected ferrocidiphenol SuccFerr transfer successfully to in vivo conditions, leading to interesting therapeutic perspectives based on this chemistry.

La maladie de Menkès est une pathologie rare d’origine génétique qui induit un déficit en cuivre fatal pour les enfants (décès avant l’âge de trois ans). Malheureusement, il n’existe à l’heure actuelle aucun traitement médicamenteux disponible sur le marché. Deux laboratoires de l’UL (le NGERE et le CITHEFOR) développent depuis 4 ans un transporteur synthétique capable de véhiculer le cuivre jusqu’au cerveau. Le nanotransporteur synthétisé est stable, biocompatible, non toxique et efficace. Une procédure réglementaire accélérée est actuellement en discussion avec l’Agence Européenne des Médicaments et le consortium espère une demande d’autorisation de mise sur le marché pour 2023.

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Un article intitulé " Physicochemical stability of azacitidine suspensions at 25 mg/mL in polypropylene syringes stored under different conditions of storage " vient de paraître dans " Molecules "

Auteurs : Quentin Trambloy, Jean Vigneron, Igor Clarot, Franck Blaise, Elise D’Huart et Béatrice Demoré

Pharmaceutical Technology in Hospital Pharmacy, 7(1), 2022.  https://doi.org/10.1515/pthp-2022-0003

Abstract

Objectives: Azacitidine is a pyrimidine nucleoside analogue whose stability is temperature dependent. Numerous publications have studied the stability of this drug with discordant results. The purpose of this work is to study the stability of azacitidine suspensions under different conditions to allow preparation in advance: vials stored at room temperature or between 2 and 8 °C, reconstituted with refrigerated water for injection (WFI) or frozen/thawed WFI, azacitidine suspensions stored at room temperature, 2–8 °C or at −20 °C. The feasibility of a vented ChemoClave® Spike vial was also tested to reconstitute and collect azacitidine to aid the preparation stage.

Methods: The stability study was performed by HPLC coupled to a photodiode array detector. The method was validated according to ICH Q2(R1). Two syringes were prepared for each analysis condition and two samples were realised for each syringe at each time of the analysis. For a storage at 2–8 °C, analyses were performed for up to 168 h. The stability was studied after 2 h at room temperature. For frozen storage, the stability was studied after 28 days.

Results: Azacitidine 25 mg/mL suspensions stored between 2 and 8 °C, prepared with refrigerated WFI or frozen/thawed WFI, retained more than 90% of the initial concentration for 96 h and then for 2 h at room temperature. Prepared with frozen/thawed WFI, azacitidine 25 mg/mL suspensions stored at −20 °C for 28 days and then 72 h between 2 and 8 °C after thawing, retained more than 90% of the initial concentration. When using a Spike system compared to using a needle for reconstitution and collection of the suspension, the results obtained by HPLC showed a decrease of 1.47% in the concentration of azacitidine. The comparisons of the volumes withdrawn after reconstitution were similar when using a Spike system or a needle.

Conclusions: Azacitidine 25 mg/mL suspensions reconstituted with refrigerated WFI were chemically stable for 4 days when stored at 2–8 °C whatever the storage of vials (refrigerator or room temperature), and 2 h at room temperature. A storage of azacitidine 25 mg/mL suspensions in syringes prepared with frozen/thawed WFI at −20 °C has been validated for up to 28 days, leading to the possibility to prepare in advance. A Spike device can be used to reconstitute and collect azacitidine.

Un article intitulé " Food-inspired innovations to improve the stability of active pharmaceutical ingredients " vient de paraître dans " International Journal of Pharmaceutics "

Auteurs : Célia Boukoufi, Ariane Boudier, Philippe Maincent, JeanVigneron, Igor Clarot

International Journal of Pharmaceutics, Volume 623, 2022, 121881. https://doi.org/10.1016/j.ijpharm.2022.121881

Abstract

Food-processing and pharmaceutical industries share a lot of stability issues against the same physical, chemical, and microbiological phenomena. They also share some solutions to improve the stability as the use of preservatives and packaging. Ecological concerns lead to the development of tremendous innovations in food. Some of these innovations could also be beneficial in the pharmaceutical domain. The objective of this review is to evaluate the potential application of these findings in the pharmaceutical field and the main limits in terms of toxicity, environmental, economic and regulatory issues. The principal factors influencing the shelf-life were highlighted through the description of the stability studies usually performed in the pharmaceutical industry (according to European guidelines). To counter those factors, different solutions are currently available as preservatives and specific packaging. They were described and debated with an overview of recent food innovations in each field. The limits of the current solutions in the pharmaceutical field and the innovation in the food field have inspired a critical pharmaceutical outlook. The active and intelligent packaging for active pharmaceutical ingredients of the future is imagined.

Un article intitulé " Gold nanostructured membranes to concentrate low molecular weight thiols, a proof of concept study" vient de paraître dans " Journal of Chromatography B "

Auteurs : Margaux Berthou, Arnaud Pallotta, Jordan Beurton, Thomas Chaigneau, Athanassia Athanassiou, Christophe Marcic, Eric Marchioni, Ariane Boudier, Igor Clarot

Journal of Chromatography B, Volume 1198, 15 May 2022, 123244. https://doi.org/10.1016/j.jchromb.2022.123244

Abstract

Thiols are very important molecules in the biomedical field involved for example in redox homeostasis. Their detection and quantification remain difficult due to their poor stability (oxidation) linked to their strong reactivity towards other thiols (by the formation of S-S bonds) or other interfering molecules in the medium. Cellulose membranes with immobilized gold nanoparticles (AuNP) were developed to capture and quantify thiols in simple and complex matrices. This device was first optimized and characterized in terms of nanostructuration and thiol adsorption. N-Acetylcysteine (NAC) and reduced glutathione (GSH), chosen as model molecules, were filtered through the device demonstrating a maximal adsorption capacity of 270 and 60 nmol respectively. In a second step, the adsorbed species were subjected to ligand exchange using a more reactive thiol, dithiothreitol. The results showed release rates of approximately 90% for NAC and GSH. Finally, the amount of endogenous GSH in rat plasma was determined without any pretreatment. For the first time to our knowledge, a nanostructured device for the capture, selective and sensitive quantification of thiols is proposed. This device is easy to handle and overcomes matrix effects. Moreover, the very large concentration factor induced by this technology will be a valuable asset to decrease the quantification limits of analytical methods.

Un article intitulé "Nitric Oxide Delivering Surfaces: An Overview of Functionalization Strategies and Efficiency Progress" vient de paraître dans " Advanced healthcare materials "

Auteurs : Jordan Beurton, Ariane Boudier, Amedea Barozzi Seabra, Nihal Engin Vrana, Igor Clarot, Philippe Lavalle

Advanced healthcare materials, 11, 13, 2022, 2102692. https://doi.org/10.1002/adhm.202102692

Abstract

An overview on the design of nitric oxide (NO) delivering surfaces for biomedical purposes is provided, with a focus on the advances of the past 5 years. A localized supply of NO is of a particular interest due to the pleiotropic biological effects of this diatomic compound. Depending on the generated NO flux, the surface can mimic a physiological release profile to provide an activity on the vascular endothelium or an antibacterial activity. Three requirements are considered to describe the various strategies leading to a surface delivering NO. Firstly, the coating must be selected in accordance with the properties of the substrate (nature, shape, dimensions…). Secondly, the releasing and/or generating kinetics of NO should match the targeted biological application. Currently, the most promising structures are developed to provide an adaptable NO supply driven by pathophysiological needs. Finally, the biocompatibility and the stability of the surface must also be considered regarding the expected residence time of the device. A critical point of view is proposed to help readers in the design of the NO delivering surface according to its expected requirement and therapeutic purpose.