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1. Ciprofloxacin loaded vascular prostheses functionalized with poly-methylbeta- cyclodextrin: The importance of in vitro release conditions

Author

Marc Bria, Nicolas Tabary, Youcef Benzine, E. Jean Baptiste, Youness Karrout, Nicolas Blanchemain, Myriem Gargouri, Mickaël Maton, Maria José Garcia-Fernandez, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 (MBLC - ADDS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Unité Matériaux et Transformations - UMR 8207 (UMET), Institut de Chimie du CNRS (INC)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL), Institut Michel Eugène Chevreul - FR 2638 (IMEC), Université d'Artois (UA)-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centrale Lille Institut (CLIL), Université de Lille, CNRS, INRA, ENSCL, Santé publique : épidémiologie et qualité des soins - EA 2694, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Advanced Drug Delivery Systems (ADDS) - U1008, Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS], Unité Matériaux et Transformations (UMET) - UMR 8207, Unité Matériaux et Transformations - UMR 8207 [UMET], Santé publique : épidémiologie et qualité des soins-EA 2694 (CERIM), Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Institut National de la Recherche Agronomique (INRA), Institut Chevreul FR2638, Université de Lille, Sciences et Technologies-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Ecole Centrale de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Université d'Artois (UA)-Université de Lille, Droit et Santé, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
poly-me beta cd, Pharmaceutical Science, 02 engineering and technology, 030226 pharmacology & pharmacy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, diffusion test, ciprofloxacin, vascular prostheses, Solubility, modified flow-through cell, Dissolution, chemistry.chemical_classification, Chromatography, Cyclodextrin, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, controlled drug delivery, In vitro, 3. Good health, Polyester, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, Polymerization, pet-me beta cd, Drug delivery, Agarose, 0210 nano-technology
Abstract

Synthetic Vascular Graft Infection (SVGI) can be very serious for patients with dramatic consequences (up to 6%). Polyester vascular grafts (PET) were modified with polymerized cyclodextrin (Poly-MeβCD) and loaded with ciprofloxacin (CFX) for the prevention of postoperative infections. The aim of this study was to investigate the CFX/Poly-MeβCD interactions and the importance of the type of the dissolution technique. The solubility of CFX was significantly improved upon Poly-MeβCD, and the interaction between CFX and Poly-MeβCD were observed by NMR (Nuclear Magnetic Resonance). Drug release was measured in phosphate buffer saline pH 7.4 at 37 °C using: (i) agitated flasks, (ii) the paddle apparatus, (iii) the conventional flow-through cells, (iv) the modified flow-through cells with agarose gel at different flow rates. Importantly, CFX release depends on the flow rate as well as the experimental set-up in vitro. CFX release from virgin prostheses (PET) was faster than from functionalized prostheses (PET-MeβCD), irrespective of the flow rate, which indicates the superiority of Poly-MeβCD in the control of CFX release. The CFX diffusion from PET-MeβCD into agarose gel showed a continuously progressive diffusion during 7 days. Thus, this test can be highly appropriate for in vitro characterization of such drug delivery systems. 53

Published
2019
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2. Bioinspired Titanium Drug Eluting Platforms Based on a Poly-β-cyclodextrin–Chitosan Layer-by-Layer Self-Assembly Targeting Infections

Author

Jonathan Sobocinski, Myriem Gargouri, Alexandra Pérez-Anes, William Laure, Feng Chai, Nicolas Tabary, Elisabeth Courcot, Joel Lyskawa, Jean-François Blach, Dennis Douroumis, Hélène Van Den Berghe, Ahmed Addad, Patrice Woisel, Nicolas Blanchemain, Bernard Martel, Université de Lille, CNRS, INRA, ENSCL, Unité Matériaux et Transformations (UMET) - UMR 8207, Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS], Unité Matériaux et Transformations - UMR 8207 [UMET], Unité de Catalyse et Chimie du Solide - UMR 8181 [UCCS], Advanced Drug Delivery Systems (ADDS) - U1008, UCCS Équipe Couches Minces & Nanomatériaux, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Centrale Lille Institut (CLIL)-Université d'Artois (UA)-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Lille-Centrale Lille Institut (CLIL)-Université d'Artois (UA)-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Lille, and Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)

Subjects
Drug, Staphylococcus aureus, Materials science, Indoles, Polymers, media_common.quotation_subject, chemistry.chemical_element, Nanotechnology, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Chitosan, chemistry.chemical_compound, Coated Materials, Biocompatible, General Materials Science, ComputingMilieux_MISCELLANEOUS, media_common, chemistry.chemical_classification, Titanium, Drug Carriers, Microbial Viability, Cyclodextrin, beta-Cyclodextrins, Polymer, Surface Plasmon Resonance, 021001 nanoscience & nanotechnology, Polyelectrolyte, 0104 chemical sciences, Anti-Bacterial Agents, chemistry, Drug delivery, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Implant, Gentamicins, 0210 nano-technology
Abstract

In the field of implantable titanium-based biomaterials, infections and inflammations are the most common forms of postoperative complications. The controlled local delivery of therapeutics from implants through polyelectrolyte multilayers (PEMs) has recently emerged as a versatile technique that has shown great promise in the transformation of a classical medical implant into a drug delivery system. Herein, we report the design and the elaboration of new biodegradable multidrug-eluting titanium platforms based on a polyelectrolyte multilayer bioactive coating that target infections. These systems were built up in mild conditions according to the layer-by-layer (L-b-L) assembly and incorporate two biocompatible polysaccharides held together through electrostatic interactions. A synthetic, negatively charged β-cyclodextrin-based polymer (PCD), well-known for forming stable and reversible complexes with hydrophobic therapeutic agents, was exploited as a multidrug reservoir, and chitosan (CHT), a naturally occurring, positively charged polyelectrolyte, was used as a barrier for controlling the drug delivery rate. These polyelectrolyte multilayer films were strongly attached to the titanium surface through a bioinspired polydopamine (PDA) film acting as an adhesive first layer and promoting the robust anchorage of PEMs onto the biomaterials. Prior to the multilayer film deposition, the interactions between both oppositely charged polyelectrolytes, as well the multilayer growth, were monitored by employing surface plasmon resonance (SPR). Several PEMs integrating 5, 10, and 15 bilayers were engineered using the dip coating strategy, and the polyelectrolyte surface densities were estimated by colorimetric titrations and gravimetric analyses. The morphologies of these multilayer systems, as well as their naturally occurring degradation in a physiological medium, were investigated by scanning electron microscopy (SEM), and their thicknesses were measured by means of profilometry and ellipsometry studies. Finally, the ability of the coated titanium multilayer devices to act as a drug-eluting system and to treat infections was validated with gentamicin, a relevant water-soluble antibiotic commonly used in medicine due to its broad bactericidal spectrum.

Published
2015
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3. PTEN expression is involved in the invasive properties of HNSCC: a key protein to consider in locoregional recurrence

Author

Béatrice Faivre, Jihane Mriouah, François Plénat, Myriem Gargouri, Cédric Boura, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Epithelial-Mesenchymal Transition, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Cell Movement, Internal medicine, Cell Line, Tumor, medicine, PTEN, Humans, RNA, Small Interfering, Cell Proliferation, Predictive marker, Oncogene, Squamous Cell Carcinoma of Head and Neck, PTEN Phosphohydrolase, Cancer, Cell migration, Cell cycle, medicine.disease, Cadherins, Head and neck squamous-cell carcinoma, Molecular medicine, Gene Expression Regulation, Neoplastic, stomatognathic diseases, Head and Neck Neoplasms, Cancer research, biology.protein, Carcinoma, Squamous Cell, Neoplasm Recurrence, Local
Abstract

International audience; Specific phenotypic effects of PTEN in head and neck squamous cell carcinoma (HNSCC) remain poorly defined without a direct causal connection between the loss of PTEN function and the progression of cancer. Here, we describe a potential role for PTEN in cancer progression. Using an shRNA targeting PTEN in HNSCC cells, we show that the loss of PTEN expression is associated with a decrease of cell adhesion, a reduction in E-cadherin expression while cell migration is promoted. Together with the tissue organization and molecular markers expressed in tumors derived from shPTEN cells in vivo, this study indicates that HNSCC cells deficient in PTEN expression undergo an epithelial‑mesenchymal transition (EMT). Additionally, our results suggest that both the low levels of expression and subcellular localization of PTEN are involved in the EMT phenotype, and ultimately in possible locoregional reccurences. We hypothesize that the loss of PTEN expression as well as the subcellular localization could be of interest as a predictive marker of recurrence in HNSCC.

Published
2013
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