2022

Article publié dans "Pharmaceutical Technology in Hospital Pharmacy"

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 The comparisons of the volumes withdrawn after reconstitution were similar when using a Spike system or a needle.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.

Article publié dans "International Journal of Pharmaceutics"

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.

Article publié dans "Journal of Chromatography B"

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.

Article publié dans "Advanced Healthcare Materials"

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.

Article publié dans "Journal of Pediatrics, Perinatology and Child Health"

Un article intitulé "High Resistance Mutation to cART in HIV-1 Exposed Infected Children and Recent Emergence of CRF02_AG Variant in Bouar, A Rural Environment of Central African Republic" vient de paraître dans "Journal of Pediatrics, Perinatology and Child Health"

Auteurs : Ulrich Vickos, Giovanni Gaiera, Nicola Cotugno, Christelle Luce Bobossi Gadia, Ornella Anne Sibiro Demi, Angelo Sala, Michela Sampaolo, Alain Le Faou, Enzo Boeri.

Journal of Pediatrics, Perinatology and Child Health, 6, 2022, 155-176. https://doi.org/10.26502/jppch.74050099

Abstract

Introduction: The emergence of HIV-1 recombinant forms and drug combined antiretroviral therapy (cART) resistance are frequent in the therapeutic course of HIV-infected children in Low and Middle-Income Countries (LMIC) precisely in Central African Republic (CAR) as evidenced by studies carried out in the Bangui capital. Vertical transmission rate including breastfeeding is 12.4. The aim is to analyze retrospectively the molecular characterization of sequencing results and mutation detected in HIV infected children under cART since infancy.

Methods: The 2019 retrospective review of the clinical, therapeutical, and immunological-molecular records of six children who were performed the genome sequencing, followed in Bouar, at the St Michel IST/HIV Center, in the north-west of the CAR. These perinatal HIV-infected children were not tested early and started late cART regimens, used for vertical transmission prevention and treatment initiation of HIV infection in CAR.

Results: We analyzed results from viral RNA extracted amplification and sequencing of 6 children plasma samples collected under first line ART. Sequencing of viral genomes revealed high level resistance mutations to NRTIs (ABC/FTC/3TC) and to NNRTIs (EFV/NVP used locally and DOR/ETR/ RPV unused) with ambiguous positions in amino-acids comparison and deletion. Three CRF02_AG strains formed a cluster by strongly detaching from other CAR and worldwide strains with robust boostrap at 91.

Conclusions: The genomes sequencing showed that resistance mutations made the treatment inefficient confirming the clinical, immunological, and virol-ogical failure and an emerging CRF02_AG genotype variant, probably of foreign origin. This discovery clearly highlights the importance of ART genetic resistance testing and personalized medicine.

 

Soutenance de thèse de doctorat : Sarah El Hajj

Sarah El Hajj soutiendra sa thèse de doctorat intitulée "Innovative screening methodology for metal chelating peptides with antioxidant properties using Surface Plasmon Resonance" dans l'amphithéatre A à l'ENSIC le mardi 22 mars à 14h. 

Article publié dans "Microorganisms"

Un article intitulé " Current Knowledge on the Oxidative-Stress-Mediated Antimicrobial Properties of Metal-Based Nanoparticles " vient de paraître dans " Microorganism "

Auteurs : Nour Mammari, Emmanuel Lamouroux, Ariane Boudier et Raphaël E. Duval

Microorganisms 2022, 10(2), 437; https://doi.org/10.3390/microorganisms10020437

Abstract

The emergence of multidrug-resistant (MDR) bacteria in recent years has been alarming and represents a major public health problem. The development of effective antimicrobial agents remains a key challenge. Nanotechnologies have provided opportunities for the use of nanomaterials as components in the development of antibacterial agents. Indeed, metal-based nanoparticles (NPs) show an effective role in targeting and killing bacteria via different mechanisms, such as attraction to the bacterial surface, destabilization of the bacterial cell wall and membrane, and the induction of a toxic mechanism mediated by a burst of oxidative stress (e.g., the production of reactive oxygen species (ROS)). Considering the lack of new antimicrobial drugs with novel mechanisms of action, the induction of oxidative stress represents a valuable and powerful antimicrobial strategy to fight MDR bacteria. Consequently, it is of particular interest to determine and precisely characterize whether NPs are able to induce oxidative stress in such bacteria. This highlights the particular interest that NPs represent for the development of future antibacterial drugs. Therefore, this review aims to provide an update on the latest advances in research focusing on the study and characterization of the induction of oxidative-stress-mediated antimicrobial mechanisms by metal-based NPs.

 

Editorial dans "Separations"

Un éditorial intitulé " Separation Methods in Biomedical Analysis, a Booming Field " vient de paraître dans " Separations "

Auteurs : Arnaud Pallotta, Ariane Boudier, Jérémie Gouyon Et Igor Clarot

Separations 2022, 9(2), 51; https://doi.org/10.3390/separations9020051

2021

Article publié dans "Health Risk Analysis"

Un article intitulé " Questioning the early events leading to the COVID-19 pandemic" vient de paraître dans " Health Risk Analysis "

Auteurs : Reis J., Frutos R., Buguet A., Le Faou A., Sandner G., Román G.C., Spencer P.S

Health Risk Analysis, 2021, no. 4, pp. 4–15. https://doi.org/10.21668/health.risk/2021.4.01.eng

Abstract

Sixteen months after the January 30, 2020 declaration by the World Health Organization of a Public Health Emergency of International Concern regarding the spread of COVID-19, SARS-CoV-2 had infected ~ 170 million humans worldwide of which > 3.5 million had died. We critically examine information on the virus origin, when and where the first human cases occurred, and point to differences between Chinese and later clinical presentations. The official patient Zero was hospitalized in Wuhan, Hubei province, China, on December 8, 2019, but retrospective analyses demonstrate prior viral circulation. Coronaviruses are present in mammals and birds, but whether a wild animal (e.g. bat, pangolin) was the source of the human pandemic remains disputed. We present two contamination models, the spillover versus the circulation model; the latter brings some interesting hypotheses about previous SARS-CoV-2 virus circulation in the human population. The age distribution of hospitalized COVID-19 patients at the start of the epidemic differed between China and the USA–EU; Chinese hospitalized patients were notably younger. The first Chinese publications did not describe anosmia-dysgeusia, a cardinal symptom of COVID-19 in Europe and USA. The prominent endothelial involvement linked with thrombotic complications was discovered later. These clinical discrepancies might suggest an evolution of the virus.

Article publié dans "Journal of Pharmaceutical Analysis"

Un article intitulé "Physicochemical degradation of phycocyanin and means to improve its stability: A short review." vient de paraître dans " Journal of Pharmaceutical Analysis "

Auteurs : Aïda Adjali, Igor Clarot, Zilin Chen, Eric Marchioni, Ariane Boudier

Journal of Pharmaceutical Analysis, 2021, 12, 3, 406-414. https://doi.org/10.1016/j.jpha.2021.12.005

Abstract

The cyanobacterium Arthrospira platensis, spirulina, is a source of pigments such as phycobiliprotein and phycocyanin. Phycocyanin is used in the food, cosmetics, and pharmaceutical industries because of its antioxidant, anti-inflammatory, and anticancer properties. The different steps involved in extraction and purification of this protein can alter the final properties. In this review, the stability of phycocyanin (pH, temperature, and light) is discussed, considering the physicochemical parameters of kinetic modeling. The optimal working pH range for phycocyanin is between 5.5 and 6.0 and it remains stable up to 45 °C; however, exposure to relatively high temperatures or acidic pH decreases its half-life and increases the degradation kinetic constant. Phycobiliproteins are sensitive to light; preservatives such as mono- and di-saccharides, citric acid, or sodium chloride appear to be effective stabilizing agents. Encapsulation within nano- or micro-structured materials such as nanofibers, microparticles, or nanoparticles, can also preserve or enhance its stability.