Actualités

L'article intitulé "Heparinized collagen-based hydrogels for tissue engineering: physical, mechanical and biological properties" vient d'être publié dans le journal "International Journal of Pharmaceutics".

Les auteurs sont : Meiling Wu, Anne Sapin-Minet, Loïc Stepan, Julien Perrin, isabelle Raet-Fries, Caroline Gaucher

Doi : https://doi.org/10.1016/j.ijpharm.2024.125126

Abstract :

As the main protein forming the vascular extracellular matrix, collagen has a weak antigenicity, making it an attractive candidate for coatings of vascular grafts. In order to bring antithrombotic properties to collagen for obtaining suitable blood compatibility of surfaces and further bioactive molecule carrying capacity, heparinization appears as a method of choice. Thus, in this article, pH-driven self-assembly was used to form collagen-based hydrogels with physical incorporation of heparins, especially low molecular weight heparin or unfractionated heparin at 1 IU/mL and 6 IU/mL. These heparinized hydrogels were evaluated for their physicochemical properties including gelation kinetic, spreading, viscoelasticity, microstructure and heparin quantification, and their biocompatibility such as cytocompatibility and their capacity to release bioactive heparins with antithrombotic properties. The loading capacity of collagen-based hydrogels was higher for unfractionated heparin (60 to 80 %) than for low molecular weight heparin (20 %). Interestingly, the highest concentration (6 IU/mL) of heparin used to form collagen-based hydrogels resulted in the formation of a softer hydrogel owning a better spreadability compared to 1 IU/mL and non heparinized collagen-based hydrogel. The 3D structure observation showed a layered formation with visible pores or spaces between the layers in all types of collagen-based hydrogels. These layers are interconnected by fibrous structures, suggesting a networked architecture. Moreover, the amount of heparin released from collagen-based hydrogel prepared with 6 IU /mL was higher than from those heparinized with 1 IU/mL attested by a delay in blood coagulation (activated partial thromboplastin time and thrombin time) and the abolishment of thrombin generation. Those hydrogels were also biocompatible, with low albumin adsorption and no impact on cell viability. Finally, heparin is retained in these hydrogels for at least seven days after cell seeding, providing the possibility of long-term antithrombotic properties. Thus, we succeeded in develop/obtain coatings with antithrombogenic properties, biocompatible and able to retain heparins at least seven days, making them good candidates with a great potential for the development and application of efficient blood-contacting materials.

L'article intitulé "Ibuprofen encapsulation inside non-conventional O/W Pickering emulsions stabilized with partially hydrophobized silica" vient d'être publié dans le journal "Frontiers in Coatings, Dyes and Interface Engineering".

Les auteurs sont : Diego Ramos, Anne Sapin-Minet, Philippe Marchal, Marianne Parent, Véronique Sadtler et Thibault Roques-Carmes

Doi : https://doi.org/10.3389/frcdi.2024.1422260

Abstract :

The encapsulation of active ingredients is an important process in various industrial sectors including pharmaceutics, foods and cosmetics. For the first time, the capacity of non-conventional anti-Bancroft oil-in-water Pickering emulsions stabilized by partially hydrophobized silica to encapsulate an apolar active is addressed. A dispersed phase volume of paraffin oil of 50% coupled to 0.5 wt.% of silica has been employed to avoid excess of silica in the continuous phase and encapsulate higher amount of ibuprofen (the model drug). Three ibuprofen contents ranging from 100 mg (1.6 mg/mL of paraffin) to 420 mg (6 mg/mL of paraffin) have been tested. The encapsulation efficiency as well as the emulsions properties are investigated by the means of light diffusion, microscopy, rheology, and HPLC coupled to mass balance. The Pickering emulsion is very efficient for the encapsulation of ibuprofen with encapsulation rates of 99% obtained inside droplets of 30 µm for all the 3 ibuprofen concentrations. This encapsulation ability is perfectly maintained, whether during ageing (during 90 days), or when the emulsion is diluted by a factor 100 inside physiological media at basic and acidic pH.

Un article intitulé "La microfluidique, un outil polyvalent en santé" vient d'être publié dans "Techniques de l'ingénieur".

Auteurs : Jérémie Gouyon, Thibault Roques-Carmes, Anne Sapin-Minet, Marianne Parent

Reférence de l'article : PHA1030 v1

Résumé :

La microfluidique est de plus en plus utilisée dans de nombreux domaines, et celui de la santé ne fait pas exception. A travers les différentes étapes de la conception d’un médicament, de la découverte d’un actif à sa formulation, l’apport de la microfluidique est illustré et discuté dans cet article. Son intérêt dans les aspects diagnostiques est également présenté. Un état des lieux large et critique fait mention des futures voies de développement abordées par les chercheurs académiciens ou industriels, ainsi que les verrous technologiques qui devront être confrontés dans les années à venir.

Un article intitulé "PBPK modeling: What is the role of CYP3A4 expression in the gastrointestinal tract to accurately predict first-pass metabolism?" vient d'être publié dans le journal "CPT-Pharmacometrics & Systems Pharmacology".

Auteurs : Justine Henriot, André Dallmann, François Dupuis, Jérémy Perrier, Sebastian Frechen

DOI :  https://doi.org/10.1002/psp4.13249

Résumé :

Gastrointestinal first-pass metabolism plays an important role in bioavailability and in drug–drug interactions. Physiologically-based pharmacokinetic (PBPK) modeling is a powerful tool to integrate these processes mechanistically. However, a correct bottom-up prediction of GI first-pass metabolism is challenging and depends on various model parameters like the level of enzyme expression and the basolateral intestinal mucosa permeability (Pmucosa). This work aimed to investigate if cytochrome P450 (CYP) 3A4 expression could help predict the first-pass effect using PBPK modeling or whether additional factors like Pmucosa do play additional roles using PBPK modeling. To this end, a systematic review of the absolute CYP3A expression in the human gastrointestinal tract and liver was conducted. The resulting CYP3A4 expression profile and two previously published profiles were applied to PBPK models of seven CYP3A4 substrates (alfentanil, alprazolam, felodipine, midazolam, sildenafil, triazolam, and verapamil) built-in PK-Sim®. For each compound, it was assessed whether first-pass metabolism could be adequately predicted based on the integrated CYP3A4 expression profile alone or whether an optimization of Pmucosa was required. Evaluation criteria were the precision of the predicted interstudy bioavailabilities and area under the concentration–time curves. It was found that none of the expression profiles provided upfront an adequate description of the extent of GI metabolism and that optimization of Pmucosa as a compound-specific parameter improved the prediction of most models. Our findings indicate that a pure bottom-up prediction of gastrointestinal first-pass metabolism is currently not possible and that compound-specific features like Pmucosa must be considered as well.

Nathan Wisniewski (2ème année de thèse de doctorat), a reçu un prix pour sa communication orale "Harvesting the Wharton’s Jelly extracellular matrix to produce a biomaterial suitable for cardiovascular tissue engineering" au congrès "Biomaterials and Biofabrication", organisé à Nancy du 16 au 17 mai 2024.

L'article intitulé "Agile quality-by-design development of alginate microparticles for encapsulation of hydrophilic drug" vient d'être publié dans "Colloids & Surfaces A : Physicochemical and Engineering Aspects".

Auteurs : Asta-Ramaha Synthia Mackin-Mohamour, Julia Budzinski, Thierry Bastogne, Thibault Roques-Carmes, Veronique Sadtler, Philippe Marchal, Anne Sapin-Minet, Marianne Parent

Doi : https://doi.org/10.1016/j.colsurfa.2024.134053

Résumé :

The development of alginate microparticles for encapsulation of hydrophilic drug is addressed. The alginate microparticles are produced by the emulsification/gelation process. The objective of this study is to optimize the encapsulation of sunset yellow, a model of small hydrophilic drug, by the means of an agile quality by design (QbD) approach. Five input factors are considered: the alginate concentration (2-7% w/V), the drug/polymer ratio (0.1/1-0.5/1), the cross-linker addition flow rate (1-1.6 mL/min), the cross-linker volume (5-10 mL), and the crosslinking time (15-60 min). Critical quality attributes (and their associated specifications) are the particle size [30-150 µm] and polydispersity, the encapsulation efficiency (>50%), and the drug loading (>10%). The implemented agile method follows three successive QbD sprints, each based on a specific design of experiments (DoE). First, a screening of the process parameters is performed using a Plackett-Burman design, followed in a second sprint by the implementation of a central composite Hartley’s design to identify the design space and to extract four eligible control operating regions where the probability to meet the CQA specifications is above 95%. In the last sprint, one of these optimal operating conditions has been qualified by testing eight end points of the region through the application of a full factorial design. This operating region corresponds to a combination of three factors: alginate concentration in [6.7;7]%, drug/polymer ratio in [0.29;0.34]w/w and a curing time in [40;60]min.

L'article intitulé "Macrophage depletion overcomes human hematopoietic cell engraftment failure in zebrafish embryo" vient d'être publié dans "Cell Death & Disease".

Auteurs : Reine El Omar, Naoill Abdellaoui, Safiatou T. Coulibaly, Laura Fontenille, François Lanza, Christian Gachet, Jean-Noel Freund, Matteo Negroni, Karima Kissa, Manuela Tavian

DOI : https://doi.org/10.1038/s41419-024-06682-x

Résumé :

Zebrafish is widely adopted as a grafting model for studying human development and diseases. Current zebrafish xenotransplantations are performed using embryo recipients, as the adaptive immune system, responsible for host versus graft rejection, only reaches maturity at juvenile stage. However, transplanted primary human hematopoietic stem/progenitor cells (HSC) rapidly disappear even in zebrafish embryos, suggesting that another barrier to transplantation exists before the onset of adaptive immunity. Here, using a labelled macrophage zebrafish line, we demonstrated that engraftment of human HSC induces a massive
recruitment of macrophages which rapidly phagocyte transplanted cells. Macrophages depletion, by chemical or pharmacological treatments, significantly improved the uptake and survival of transplanted cells, demonstrating the crucial implication of these innate immune cells for the successful engraftment of human cells in zebrafish. Beyond identifying the reasons for human hematopoietic cell engraftment failure, this work images the fate of human cells in real time over several days in macrophage-depleted zebrafish embryos.

Ajourd'hui à 14h30, le Pr Nicolas Blanchemain de l'UFR3S - Pharmacie, Université de Lille, donnera une conférence au sein de l'unité pour présenter ses travaux intitulés "Biomatériaux à libération prolongée de principes actifs, design et évaluation in vitro / in vivo".

Rama Alhasan soutiendra sa thèse de doctorat intitulée "Nouveaux composés organoséléniés : du cœur du thon aux capacités antioxydantes en passant par la signalisation complexe de monoxyde d'azote (selenox)" le mardi 16 avril à 14h, dans la salle de réunion de l'unité de recherche.

Le jury est composé de :

- Directeur de thèse : Mme Caroline Gaucher, Pr, Université de Lorraine, UR 3452 CITHEFOR, Nancy, France

- Co-directeur de thèse : Mr Claus Jacob, Pr, Universität des Saarlandes, Saarbrücken, Allemagne

- Rapporteur : Mr Mourad Elhabiri, Dr, CNRS, ECPM, Université de Strasbourg. Strasbourg, France

- Rapporteur : Mme Elke Richling, Pr, Technische Universität Kaiserslautern, Kaiserslautern, Allemagne

- Examinateur : Mme Sandrine Boschi-Muller, Pr, IMoPA, Université de Lorraine, Nancy, France

- Invités : 

Mr Stefan Boettcher, Dr, Universität des Saarlandes, Saarbrücken, Allemagne

Mme Caroline Perrin-Sarrado, Dr, CITHEFOR EA 3452, Université de Lorraine, Nancy, France

Mr Bruce Morgan, Pr, Universität des Saarlandes, Saarbrücken, Allemagne

Ce soir à partir de 20h30 Anne Sapin-Minet et Marianne Parent seront interviewées par Fabien Bornes au sujet du jeu sérieux développé pour enseigner les nanotechnologies aux étudiants en 3ème année de pharmacie et des activités de recherche.

Cliquez ici pour suivre le direct sur la chaîne Twich de Fabien Bornes !