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7. Succinimido–Ferrocidiphenol Complexed with Cyclodextrins Inhibits Glioblastoma Tumor Growth In Vitro and In Vivo without Noticeable Adverse Toxicity

Author

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

Published
2022
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17. Acceptability of oral liquid pharmaceutical products in older adults: palatability and swallowability issues

Author

Belissa, Emilie, primary, Vallet, Thibault, additional, Laribe-Caget, Sandra, additional, Chevallier, Alain, additional, Chedhomme, François-Xavier, additional, Abdallah, Fattima, additional, Bachalat, Nathalie, additional, Belbachir, Sid-Ahmed, additional, Boulaich, Imad, additional, Bloch, Vanessa, additional, Delahaye, Anne, additional, Depoisson, Mathieu, additional, Wojcicki, Amélie Dufaÿ, additional, Gibaud, Stéphane, additional, Grancher, Anne-Sophie, additional, Guinot, Caroline, additional, Lachuer, Celia, additional, Lechowski, Laurent, additional, Leglise, Patrick, additional, Mahiou, Abdel, additional, Meaume, Sylvie, additional, Michel, Corinne, additional, Michelon, Hugues, additional, Orven, Yann, additional, Perquy, Ines, additional, Piccoli, Matthieu, additional, Rabus, Maïté, additional, Ribemont, Annie-Claude, additional, Rwabihama, Jean-Paul, additional, Trouvin, Jean-Hugues, additional, Ruiz, Fabrice, additional, and Boudy, Vincent, additional

Published
2019
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21. CHAPTER 8. Arsenic-based Anticancer Agents

Author

Gibaud, Stéphane, Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), Casini, Angela, Vessières, Anne, and Meier-Menches, Samuel M

Subjects
[SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Arsenic-based drugs were widely used in the treatment of infectious diseases in the 1900s, but cancer treatment has advanced with the marketing of Trisenox® (INN: arsenic trioxide) for treatment of acute promyelocytic leukemia in the 2000s. In this chapter, I first review the history of the treatment of cancer by arsenic. In the 17th century, some physicians were convinced that an external application of powder could reduce breast cancer cells. Those adventurous applications led only to tissue necrosis, and we now understand how dangerous it was for the patient. An important step forward was also made with Fowler's solution, which would be orally administered. Afterwards, Cutler and Bradford demonstrated that this solution drastically reduced the number of neutrophils in myelogenous leukemia. The more recent marketing of Trisenox® and its unique efficacy in the treatment of acute promyelocytic leukemia raised questions about the mechanism of action of arsenic in cancer treatment. Finally, this chapter summarizes the major mechanisms that lead to the reduction in growth and proliferation of cancer cells. At a molecular level, arsenic is thought to link to numerous proteins (i.e., via the thiol groups of the amino acid side-chains). We know now that some very specific targets exist that are worthy of study.

Published
2019

24. Auteurs de la 5e édition

Author

Renaudin Pierre, Batisse Marie, Bernard-Arnoux Florian, Lehmann Audrey, Goehringer François, Nivoix Yasmine, Ratsimbazafy Voa, Limat Samuel, Bacle Astrid, Burgos Leon Cécile, Mary Aurélien, Csajka Chantal, Baudrant Magalie, Prot-Labarthe Sonia, Charmillon Alexandre, Bardet Jean-Didier, Trout Hervé, Grellet Jean, Bréant Valentine, Janoly-Dumenil Audrey, Roustit Matthieu, Bernard Lise, Buyse Marion, Gueneau Pauline, Pulcini Céline, Levêque Dominique, Hallit Souheil, Sallerin Brigitte, Bertrand Marie-Anne, Terrier-Lenglet Aurélie, Navas Dominique, Nerich Virginie, Bertin Philippe, Venisse Sandrine, Kaiser Jean-Daniel, Sebahoun Pascale, Venisse Nicolas, Pagès Arnaud, Mercié Martial, Calop Nathalie, Manuelli Marine, Asseray Nathalie, Dine Thierry, Gibaud Stéphane, Brion Françoise, Chautant Fiona, Mondoloni Pauline, Cazin Jean-Louis, Dupuis Antoine, Huon Jean-François, Bochaton Thomas, Sautou Valérie, Calop Jean, Sabatier Brigitte, Diehl Jean-Luc, Breilh Dominique, Korb-Savoldelli Virginie, Chanoine Sébastien, Clairet Anne-Laure, Fernandez Christine, Jouanny Pierre, Meyer Florence, Mornex Jean-François, Mongaret Kossmann Céline, Vergne-Salle Pascale, Laborde Charlotte, Gérard Blandine, Capelle Aude, Guignard Bertrand, Salameh Pascale, Kodjikian Laurent, Honoré Stéphane, Mille Frédéric, Calvet Pauline, Aulagner Gilles, Tron Camille, Fagnoni Philippe, Moulin Philippe, Binson Guillaume, Boulieu Roselyne, Bugnon Olivier, Pin Isabelle, Marie Nicolas, Bonhomme-Faivre Laurence, Derimay François, Pison Christophe, Montani David, Fardellone Patrice, Leroy Joël, Castet-Nicolas Audrey, Larger Magali, Rouault Anne, Korb Diane, Dode Xavier, Naudet Florian, Dousset Virginie, Sebbag Laurent, Ragot Stéphanie, Peyrière Hélène, Grare Marion, Fournel Alexandra, Hindlet Patrick, Bonvin Aurélie, Potin Sophie, Reix Philippe, Aparicio Thomas, Herbrecht Raoul, Duval Raphaël, Ubeaud-Séquier Geneviève, Boursier Amélie, Le Turnier Paul, Lebargy François, Hajj Aline, Bedouch Pierrick, Armoiry Xavier, Bourdon Olivier, Vukusic Sandra, Boulin Mathieu, Malet Louise, Puisset Florent, Cestac Philippe, Rouch Laure, Barrail-Tran Aurélie, Caron Philippe, Béjot Yannick, Tauveron Igor, Brazier Michel, Lemaitre Florian, Demoré Béatrice, Bonnabry Pascal, Ottomani Hélène, Ploteau Stéphane, Monnot Tess, Potie Laudine, Jost Jeremy, Beney Johnny, Chapuis Claire, Le Moal Gwenaël, Sacre Hala, Hansel-Esteller Sylvie, Bourcier Elsa, Quillet Pauline, Chekroud Hacène, Allenet Benoît, and Ragon Alain

Published
2018

30. Organoarséniés dérivés du 2-phényl- [1,3,2]dithiarsolane-4-yl)-méthanol (AsIII) à propriétés antileucémiques : des trypanosomicides aux anticancéreux

Author

Gibaud, Stéphane, Astier, A., Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), and Université de Lorraine (UL)

Subjects
MESH: Humans, Leukemia, MESH: Leukemia, MESH: Arsenicals, MESH: Antineoplastic Agents, Animals, Humans, MESH: Animals, Antineoplastic Agents, MESH: Trypanocidal Agents, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Trypanocidal Agents, Arsenicals
Abstract

International audience; For several decades, organometallic and organometalloid compounds have played an important part in anticancer chemotherapies, in particular those derived from platinum. Trivalent arsenic, in the form of arsenic trioxide (As2O3; Trisenox(R)) is currently used in the treatment of refractory leukemias, but at the cost of major adverse effects. Moreover, recent studies showed that the trypanocide melarsoprol, could be more effective than arsenic trioxide on myelogenous leukaemias. We have synthesized a series of derivatives from 2-phenyl-[1,3,2]dithiarsolan-4-yl)-methanol (AsIII). Our work shows that the substitution of the aromatic ring by an iodine atom in the ortho position or by an amino-dimethoxytriazin group in the para position increases very significantly the antileukemic activity and improves the therapeutic index (IT=LD50/IC50) of these melarsoprol-derivatives molecules, as compared to arsenic trioxide. However, one of the most promising compounds seems to be arsthinol, an old drug used in the past as an amebicide. Nanoparticle carriers of melarsoprol were also prepared for the purpose of modifying its tissue distribution reduce its brain toxicity.

Published
2007

31. Synthesis of S -nitrosoglutathione-alginate for prolonged delivery of nitric oxide in intestines.

Author

Shah, Shefaat Ullah, Socha, Marie, Fries, Isabelle, and Gibaud, Stéphane

Subjects
DISEASES, ALGINATES, CROHN'S disease, GLUTATHIONE, POLYMERS
Abstract

S-nitrosothiols are a class of NO-donors currently under investigation for the treatment of various diseases. In this study, we developed a novel NO-donor (S-nitrosoglutathione-alginate, SNA) by cross-linking alginate withS-nitrosothiols, which can deliver NO in a sustained manner. This compound can be further evaluated for oral delivery to treat Crohn’s disease. This new compound was prepared using a two-step procedure involving (I) linkage of reduced glutathione to alginate and (II) post-nitrosation with sodium nitrite (NaNO2). The amount of linked thiol moieties for the possible nitrosation was calculated using Ellman’s method, and the amount of NO abducted on the polymer was calculated using the Griess–Saville method. Anex vivomodel (i.e. Ussing chamber) was used to investigate the permeation of this new NO-donor across the rat intestinal barrier. We obtained polymers with different numbers of abducted NOs (174 ± 21 μmol/g for SNA F1 and 468 ± 23 μmol/g for SNA F2) depending on the procedure used for nitrosation. In theex vivostudies in the Ussing chamber, SNA F2 exhibited a sustained release for at least 10 h. The effect of pH on the stability of the new compound was also investigated, and the new compound was more stable at a mildly basic pH of 8.4 where 73% remained after 1 week. However, only 50% remained after 1 week at an acidic pH of 1.2. In the cytotoxicity studies (Caco2), this compound was nontoxic at concentrations of less than 200 μM. [ABSTRACT FROM PUBLISHER]

Published
2016
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33. Thiomers and their potential applications in drug delivery

Author

Shah, Kifayat Ullah, Shah, Shefaat Ullah, Dilawar, Naz, Khan, Gul Majid, and Gibaud, Stéphane

Abstract

ABSTRACTIntroduction: Thiomers are the product of the immobilization of sulfhydryl-bearing ligands onto the polymer backbone of a conventional polymer, which results in a significant improvement in mucoadhesion; in situgelation and efflux inhibition compare with unchanged polymers. Because of thiol groups, thiomers have more reactivity and enhanced protection against oxidation. Since the late 1990s, extensive work has been conducted on these promising polymeric excipients in the pharmaceutical field.Areas covered: This review covers thiomers, their classification and their different properties. Various techniques for the synthesis, purification and characterization of thiomers are described in detail. This review also encompasses their various properties such as mucoadhesion, permeation enhancement, in situgelation and efflux inhibition, as well as different formulations based on thiomers. In addition to the use of thiomers as multifunctional excipients, this review also encompasses their use as drugs.Expert opinion: The synthesis is realized by linkage of sulfhydryl-bearing ligands but reported methods give low yields. Higher degrees of modification are not necessary and would probably lead to extreme changes in properties. Nevertheless, an accurate characterization of the final product is important. The scale-up procedure for industrial manufacturing has been adapted to produce GMP materials; Lacrimera® eye drops have already entered the European market.

Published
2017
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37. Choc septique lors de méningites à Haemophilus influenzae. Choix de l'antibiothérapie. 5èmes Journées de l'Internat des hôpitaux de Paris Ile-de-France, Biologie médicale et Pharmacie, 4 5 Décembre 1991, Paris Nord Villepinte

Author

Gibaud, Stéphane, Bennahni, H., Goury, V., Vincent, Florence, Bingen, E, Darbord, J, Pharmacie Clinique - Nancy, Faculté de Pharmacie, Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), Centre National de la Recherche Scientifique (CNRS), and Université de Provence - Aix-Marseille 1

Subjects
[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication
Published
1991

41. Synthesis and characterization of S-nitrosoglutathione-oligosaccharide-chitosan as a nitric oxide donor

Author

Shah, Shefaat Ullah, Martinho, Nuno, Socha, Marie, Pinto Reis, Catarina, and Gibaud, Stéphane

Abstract

Objectives:The aim of this work is to synthesize a novel stable and biodegradable nitric oxide (NO) donor polymer based on a chitosan backbone. This polymer needed to be linked to glutathione (GSH), which was nitrosated in a second step. This polymer has been developed as an NO delivery platform that could be further evaluated for an oral delivery in Crohn’s disease.Methods:The new polymer (named S-nitrosoglutathione-oligosaccharide-chitosan or SNOC) was obtained using a two-step procedure involving the linkage of GSH to chitosan via an amidine reaction followed by a post-nitrosation with NaNO2. The GSH linkage was assessed using NMR, FTIR and an Ellman’s test, whereas the final NO amount was determined by the Griess and Saville method.Results: Polymers with different numbers of NO groups were obtained (159.04 ± 64.16 µmol/g of polymer for SNOC G1 and 525.08 ± 151.35 µmol/g of polymer for SNOC G2) depending on the procedure used for production. When tested in an Ussing chamber, SNOC G2 had a sustained release of NO and nitrites for at least 6 h.Conclusion: We believe that this type of polymer is adapted for the development of various formulations, including microparticles.

Published
2015
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42. LES AUTEURS

Author

ALLENET, Benoît, APARICIO, Thomas, ARMOIRY, Xavier, AULAGNER, Gilles, BALLEREAU, Françoise, BARDET, Jean-Didier, BARRAIL-TRAN, Aurélie, BATISSE, Marie, BAUDRANT, Magalie, BEDOUCH, Pierrick, BENEY, Johnny, BERTAND, Marie-Anne, BEVILACQUA, Sibylle, BONHOMME-FAIVRE, Laurence, BONNABRY, Pascal, BONVIN, Aurélie, BOULIEU, Roselyne, BOULIN, Mathieu, BOURDON, Olivier, BOUTOILLE, David, BOYER-GRAND, Anne, BRAZIER, Michel, BRÉANT, Valentine, BREILH, Dominique, BREUKER, Cyril, BRION, Françoise, BRUNET, Philippe, BUGNON, Olivier, BURGOS LEON, Cécile, BUYSE, Marion, CABARET, Blandine, CALOP, Jean, CALOP, Nathalie, CARON, Philippe, CASTET-NICOLAS, Audrey, CERTAIN, Agnès, CESTAC, Philippe, CHANOINE, Sébastien, CHAPUIS, Claire, CHEKROUD, Hacène, CHOPINEAU, Jean, CHOUCHANE, Nabil, CSAJKA, Chantal, DALLEUR, Olivia, DAVRINCHE, Catherine, DEJEAN, Catherine, DEMORÉ, Béatrice, DIEHL, Jean-Luc, DI MARTINO, Cyrille, DINE, Thierry, DODE, Xavier, DOUSSET, Virginie, DUPUIS, Antoine, DUVAL, Raphaël, FAGNONI, Philippe, FARDELLONE, Patrice, FARINOTTI, Robert, FERNANDEZ, Christine, FERREIRA, Ema, FOUCHER, Nadine, GIBAUD, Stéphane, GIRARD-TOURNILHAC, Isabelle, GOURDIER, Bertrand, GRARE, Marion, GRELLET, Jean, GUICHARD, Sylvie, GUIGNARD, Bertrand, HANSEL-ESTELLER, Sylvie, HERBRECHT, Raoul, HINDLET, Patrick, HUET, Estelle, IVANES, Fabrice, JAAFARI, Nematollah, KAISER, Jean-Daniel, KARNIB AMAL, Al-Hajje, KALTENBACH, Matthieu, KODJIKIAN, Laurent, LACOUR, Valérie, LARGER, Magali, LEBARGY, François, LEHMANN, Audrey, LEMAITRE, Florian, LE MOAL, Gwenaël, LEROY, Joël, LEVÊQUE, Dominique, LIMAT, Samuel, LOPES, Patrice, LUYCKX, Michel, MAILHOT, Claude, MALLET, Louise, MARQUET, Aurélie, MARY, Aurélien, METZ, Damien, MILLE, Frédéric, MONTANI, David, MORIN, Caroline, MORNEX, Jean-François, NAVAS, Dominique, NERICH, Virginie, NIVOIX, Yasmine, OLLIVIER, Florence, OUAHCHI, Zeineb, PAYSANT, Mélanie, PEYRIÈRE, Hélène, PHARAND, Chantal, PIN, Isabelle, PISON, Christophe, POTIE, Laudine, PROT-LABARTHE, Sonia, PUISSET, Florent, RAGON, Alain, REIX, Philippe, REY, Evelyne, RICHARD, Denis, ROUAULT, Anne, ROUSTIT, Matthieu, SABATIER, Brigitte, SALAMEH, Pascale, SALLERIN, Brigitte, SAMAR, Rachidi, SANAA, Awada, SAUTOU-MIRANDA, Valérie, SAUX, Marie-Claude, SEBBAG, Laurent, SENON, Jean-Louis, SHOUSHA, Sherif, SIBELLAS, Franck, SPINEWINE, Anne, TAUVERON, Igor, TROUT, Hervé, TULKENS, Paul M., UBEAUD-SÉQUIER, Geneviève, VACHER-COPONAT, Henri, VENISSE, Nicolas, VENISSE, Sandrine, VUKUSIC, Sandra, WILLIAMSON, David, WORONOFF-LEMSI, Marie-Christine, and ZAKIA HARZALLAH, Inès

Published
2012
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43. Poly(ϵ-caprolactone) and Eudragit® microparticles containing fludrocortisone acetate

Author

Gibaud, Stéphane, Jabir Al Awwadi, Najim, Ducki, Camille, and Astier, Alain

Subjects
*HORMONE therapy, *CAPROLACTAM, *NANOPARTICLES, *DRUG side effects
Abstract

Substitutive hormonal therapies have to be administered for long periods. Thus, the development of sustained-release forms, as microparticle suspensions, is interesting in order to improve patient compliance by reducing dosing frequencies and side effects. The aim of this work was to compare different formulations of fludrocortisone microparticles for the treatment of mineralocorticoid insufficiency. The study was done with different polymers (poly(ϵ-caprolactone), Eudragit® RS and Eudragit® RL) and different processes (O/W solvent evaporation methods and S/O/W evaporation methods). The use of a suspension of micronized drug in dichloromethane as dispersed phase (S/O/W method) significantly improved the process. Whereas low concentrations of FLU dissolved in the dispersed phase led to smooth-surface homogeneous microparticles and poor incorporation efficiency (5.8–7.3%); suspensions of FLU led to microparticles with numerous crystals on their surfaces (S/O/W microparticles) and high incorporation efficiency (about 79%). However, the best release profiles were obtained with microparticles prepared with 7.5 mg/ml of dichloromethane, near saturation. Moreover, the use of mixtures of poly(ϵ-caprolactone), Eudragit® RS and RL did not improve the release profiles. [Copyright &y& Elsevier]

Published
2004
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44. Evolution of Bordetella pertussis over a 23-year period in France, 1996 to 2018

Author

Bouchez, Valérie, Guillot, Sophie, Landier, Annie, Armatys, Nathalie, Matczak, Soraya, Toubiana, Julie, Brisse, Sylvain, Brieu, Nathalie, Hamdad, Farida, Kempf, Marie, Pailhoriès, Hélène, Jensen, Cécile, Lehours, Philippe, Guiraud, Jennifer, Le Bars, Hervé, Isnard, Christophe, Wilhelm, Nathalie, Le Coustumier, Alain, Delmas, Julien, De Briel, Dominique, Souply, Laurent, Aberrane, Saïd, Coudé, Marie, Garnier, Fabien, Descours, Ghislaine, Jean-Pierre, Hélène, Alauzet, Corentine, Gibaud, Sophie-Anne, Bonacorsi, Stéphane, Brasme, Lucien, Lemée, Ludovic, Koebel, Christelle, Lanotte, Philippe, Bland, Stéphane, Petitprez, Hélène, Raffenot, Didier, Levast, Marion, Doucet-Populaire, Florence, Bourgeois-Nicolaos, Nadège, Burucoa, Christophe, Grattard, Florence, Marque-Juillet, Stéphanie, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], Centre national de Référence de la Coqueluche et autres Bordetelloses - National Reference Center for Whooping Cough and other Bordetella infections (CNR), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), This work was performed with the financial support of the Institut Pasteur and of Santé Publique France., French pertussis microbiology study group: Nathalie Brieu, Farida Hamdad, Marie Kempf, Hélène Pailhoriès, Cécile Jensen, Philippe Lehours, Jennifer Guiraud, Hervé Le Bars, Christophe Isnard, Nathalie Wilhelm, Alain Le Coustumier, Julien Delmas, Dominique De Briel, Laurent Souply, Saïd Aberrane, Marie Coudé, Fabien Garnier, Ghislaine Descours, Hélène Jean-Pierre, Corentine Alauzet, Sophie-Anne Gibaud, Stéphane Bonacorsi, Lucien Brasme, Ludovic Lemée, Christelle Koebel, Philippe Lanotte, Stéphane Bland, Hélène Petitprez, Didier Raffenot, Marion Levast, Florence Doucet-Populaire, Nadège Bourgeois-Nicolaos, Christophe Burucoa, Florence Grattard, Stéphanie Marque-Juillet, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Collège Doctoral, Université Paris Cité (UPCité), and Institut Pasteur [Paris]-Institut Pasteur [Paris]

Subjects
Serotype, Bordetella pertussis, population evolution, Whooping Cough, Epidemiology, [SDV]Life Sciences [q-bio], Fimbria, MESH: Pertussis Toxin, MESH: Virulence Factors, Bordetella, Pertussis toxin, Microbiology, pertactin, MESH: Bordetella pertussis, 03 medical and health sciences, 0302 clinical medicine, Antigen, Virology, MESH: Child, medicine, Humans, Virulence Factors, Bordetella, 030212 general & internal medicine, Child, Whooping cough, 030304 developmental biology, Pertussis Vaccine, vaccine antigen deficiency, 0303 health sciences, Surveillance, MESH: Humans, biology, MESH: Bacterial Outer Membrane Proteins, Public Health, Environmental and Occupational Health, MESH: Whooping Cough, biology.organism_classification, medicine.disease, fimbriae serotype, 3. Good health, respiratory tract diseases, Vaccination, MESH: France, Pertussis Toxin, MESH: Pertussis Vaccine, France, Pertactin, Bacterial Outer Membrane Proteins
Abstract

Background Bordetella pertussis is the main agent of whooping cough. Vaccination with acellular pertussis vaccines has been largely implemented in high-income countries. These vaccines contain 1 to 5 antigens: pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and/or fimbrial proteins (FIM2 and FIM3). Monitoring the emergence of B. pertussis isolates that might partially escape vaccine-induced immunity is an essential component of public health strategies to control whooping cough. Aim We aimed to investigate temporal trends of fimbriae serotypes and vaccine antigen-expression in B. pertussis over a 23-year period in France (1996–2018). Methods Isolates (n = 2,280) were collected through hospital surveillance, capturing one third of hospitalised paediatric pertussis cases. We assayed PT, FHA and PRN production by Western blot (n = 1,428) and fimbriae production by serotyping (n = 1,058). Molecular events underlying antigen deficiency were investigated by genomic sequencing. Results The proportion of PRN-deficient B. pertussis isolates has increased steadily from 0% (0/38) in 2003 to 48.4% (31/64) in 2018 (chi-squared test for trend, p 481 insertion within the prn gene or a 22 kb genomic inversion involving the prn promoter sequence, indicative of convergent evolution. FIM2-expressing isolates have emerged since 2011 at the expense of FIM3. Conclusions B. pertussis is evolving through the rapid increase of PRN-deficient isolates and a recent shift from FIM3 to FIM2 expression. Excluding PRN, the loss of vaccine antigen expression by circulating B. pertussis isolates is epidemiologically insignificant.

Published
2021

45. A Decision Support Tool Facilitating Medicine Design for Optimal Acceptability in The Older Population

Author

Anne Delahaye, Stéphane Gibaud, Anne-Sophie Grancher, Vincent Boudy, Sandra Laribe-Caget, Corinne Michel, Alain Chevallier, Sylvie Meaume, Matthieu Piccoli, Vanessa Bloch, François-Xavier Chedhomme, Thibault Vallet, Amélie Dufaÿ-Wojcicki, Annie-Claude Ribemont, Fattima Abdallah, Imad Boulaich, Maite Rabus, Patrick Leglise, Laurent Lechowski, Ines Perquy, Abdel Mahiou, Fabrice Ruiz, Emilie Belissa, Yann Orven, Nathalie Bachalat, Mathieu Depoisson, Sid-Ahmed Belbachir, Caroline Guinot, Celia Lachuer, Hugues Michelon, Jean-Paul Rwabihama, Jean-Hugues Trouvin, Laboratoire Conception de Produits et Innovation (LCPI), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM), ClinSearch [Malakoff, France], Agence Générale des Equipements et Produits de Santé [Paris] (AGEPS), Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], CHU Henri Mondor, Hôpital Sainte Perine [AP-HP], Centre de Biochimie Structurale [Montpellier] (CBS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Université Paris Descartes - Paris 5 (UPD5), Hôpital Vaugirard-Gabriel Pallez, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), Centre Hospitalier de l’Ouest Vosgien [Neufchâteau] (CHOV), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, Hôpital Rothschild, AP-HP Hôpital Sainte Perine, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Biologie et Génétique des Interactions Plante-Parasite (UMR BGPI), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA), Groupe Hospitalier Avicenne-Jean Verdier-René Muret, Gibaud, Stéphane, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Multivariate statistics, Decision support system, Aging, Multivariate analysis, Computer science, Applied psychology, Judgement, Pharmaceutical Science, 030226 pharmacology & pharmacy, 01 natural sciences, 010104 statistics & probability, Random Allocation, 0302 clinical medicine, Pharmacology (medical), Prospective Studies, Reliability (statistics), Aged, 80 and over, education.field_of_study, 3. Good health, medicine acceptability, multivariate analysis, Molecular Medicine, Female, Biotechnology, Research Paper, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, swallowability, Population, Pharmacy, [SDV.SP.PG] Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, elderly, Decision Support Techniques, Medication Adherence, 03 medical and health sciences, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Humans, 0101 mathematics, education, Aged, Pharmacology, business.industry, Organic Chemistry, drug formulation, Cross-Sectional Studies, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, Drug Design, Polypharmacy, Observational study, business
Abstract

International audience; PurposeMedicine acceptability, which is of the utmost importance for vulnerable patients’ adherence, is driven by both user and product characteristics. Herein, a novel multivariate approach integrating the many aspects of acceptability is used to discriminate positively and negatively accepted medicines in the older population.MethodsAn observational study was carried out in eight hospitals and eight nursing homes to collect a large set of real-life data on medicines uses in older patients (≥65 years). Mapping and clustering explored these multiple observational measures and summarised the main information into an intelligible reference framework. Resampling statistics were used to validate the model’s reliability.ResultsA three-dimensional map and two clusters defining acceptability profiles, as positive or negative, emerged from the 1079 evaluations. Factors of interest (medicines, user features…) were positioned on the map at the barycentre of their evaluations and assigned to an acceptability profile. Focusing on patients’ ability to swallow, we have highlighted the tool’s efficacy in demonstrating the impact of user features on medicine acceptability.ConclusionsThis multivariate approach provides a relevant judgement criterion for this multi-dimensional concept. Facilitating the choice of the most appropriate dosage form to achieve optimal acceptability in a targeted population, this tool is of real potential to improve clinical decisions.

Published
2018

46. Preparation of 3,4-diaminopyridine microparticles by solvent-evaporation methods

Author

Aurélie Bonneville, Alain Astier, Stéphane Gibaud, Gibaud, Stéphane, Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), and Université de Lorraine (UL)

Subjects
MESH: Microscopy, Electron, Scanning, MESH: Delayed-Action Preparations, Scanning electron microscope, Drug Compounding, Polyesters, MESH: Microspheres, Acrylic Resins, Pharmaceutical Science, MESH: Solvents, 030226 pharmacology & pharmacy, Dosage form, Excipients, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Polymer chemistry, MESH: Particle Size, 4-Aminopyridine, Particle Size, Microparticle, MESH: Excipients, Dichloromethane, MESH: Acrylic Resins, Aqueous two-phase system, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Polyesters, Microspheres, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, MESH: 4-Aminopyridine, chemistry, Delayed-Action Preparations, MESH: Drug Compounding, Polycaprolactone, Microscopy, Electron, Scanning, Solvents, Amifampridine, Drug carrier, Caprolactone, 030217 neurology & neurosurgery, Nuclear chemistry
Abstract

International audience; The present study compares two methods of preparation of microparticles of 3,4-diaminopyridine (3,4-DAP) for the treatment for multiple sclerosis and Lambert-Eaton myasthenia syndrome. Poly( epsilon -caprolactone) microparticles were prepared with a solvent-evaporation W/O method. The 3,4-DAP was dispersed in dichloromethane, leading to a suspension. The dispersion and the solidification of the dichloromethane droplets in an aqueous phase have led to microparticles of 55.3+/-34.7 microm. The incorporation of the drug by milligram of powder was very low (1.91 micrograms/mg) and the scanning electron microscopy (SEM) did not show any crystal but marks of dissolved crystals were observed on the polymeric surface. EudragitRS microspheres containing 3,4-DAP were prepared by a solvent-evaporation technique using light mineral oil as continuous phase. The drug and the polymer were completely dissolved in an acetone solution, used as discontinuous phase. This formulation have led to a higher incorporation of the drug (88.25 micrograms/mg). The particle size was 91.8+/-44.3 microm. The observation, by SEM, shows many crystals on the surface and inside the microparticles. A slow-release of the drug in a phosphate buffer pH 7.4 was observed (50% in 60 min and about 70% in 4 h).

Published
2002

47. Poly(epsilon-caprolactone) and Eudragit microparticles containing fludrocortisone acetate

Author

Camille Ducki, Najim Jabir Al Awwadi, Stéphane Gibaud, Alain Astier, Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), and Gibaud, Stéphane

Subjects
Stereochemistry, MESH: Delayed-Action Preparations, Chemistry, Pharmaceutical, Polyesters, Pharmaceutical Science, Dosage form, Suspension (chemistry), chemistry.chemical_compound, MESH: Chemistry, Pharmaceutical, Polymethacrylic Acids, MESH: Fludrocortisone, MESH: Particle Size, Particle Size, Microparticle, Dichloromethane, chemistry.chemical_classification, MESH: Polymethacrylic Acids, Fludrocortisone Acetate, Polymer, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Polyesters, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, chemistry, Delayed-Action Preparations, Fludrocortisone, Polycaprolactone, Caprolactone, Nuclear chemistry
Abstract

International audience; Substitutive hormonal therapies have to be administered for long periods. Thus, the development of sustained-release forms, as microparticle suspensions, is interesting in order to improve patient compliance by reducing dosing frequencies and side effects. The aim of this work was to compare different formulations of fludrocortisone microparticles for the treatment of mineralocorticoid insufficiency. The study was done with different polymers (poly(epsilon-caprolactone), Eudragit RS and Eudragit RL) and different processes (O/W solvent evaporation methods and S/O/W evaporation methods). The use of a suspension of micronized drug in dichloromethane as dispersed phase (S/O/W method) significantly improved the process. Whereas low concentrations of FLU dissolved in the dispersed phase led to smooth-surface homogeneous microparticles and poor incorporation efficiency (5.8-7.3%); suspensions of FLU led to microparticles with numerous crystals on their surfaces (S/O/W microparticles) and high incorporation efficiency (about 79%). However, the best release profiles were obtained with microparticles prepared with 7.5 mg/ml of dichloromethane, near saturation. Moreover, the use of mixtures of poly(epsilon-caprolactone), Eudragit RS and RL did not improve the release profiles.

Published
2004

48. Polyalkylcyanoacrylate nanoparticles as carriers for granulocyte-colony stimulating factor (G-CSF)

Author

Patrick Couvreur, Jean-Paul Andreux, Colette Weingarten, C Rousseau, R Favier, L Douay, Stéphane Gibaud, Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), Département de Mathématiques et de statistique [UdeM- Montréal] (DMS), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Bioénergétique fondamentale et appliquée, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physico-chimie, pharmacotechnie, biopharmacie (PCPB), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), and Gibaud, Stéphane

Subjects
Pharmaceutical Science, Nanoparticle, 02 engineering and technology, Mice, 03 medical and health sciences, In vivo, Granulocyte Colony-Stimulating Factor, Animals, Humans, MESH: Animals, Cyanoacrylates, MESH: Mice, 030304 developmental biology, MESH: Cyanoacrylates, Drug Carriers, 0303 health sciences, MESH: Humans, Chemistry, fungi, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 021001 nanoscience & nanotechnology, Recombinant Proteins, In vitro, Granulocyte colony-stimulating factor, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Drug Carriers, Anionic addition polymerization, Polymerization, Biochemistry, Liberation, Female, MESH: Granulocyte Colony Stimulating Factor, Recombinant, 0210 nano-technology, Drug carrier, MESH: Female
Abstract

International audience; The human recombinant granulocyte colony-stimulating factor (rhG-CSF) is largely used in the treatment of neutropenia occurring during chemotherapy. After injection, this glycoprotein distributes through the whole body. Thus, to obtain high and durable bone marrow concentrations, targeting with polyalkylcyanoacrylate nanoparticles was considered. Two methods of preparation were investigated: anionic polymerization and precipitation of the preformed polymer. By anionic polymerization, it was possible to associate more than 66% of rhG-CSF with nanoparticles (polyisobutyl- or polyisohexylcyanoacrylate nanoparticles) when the glycoprotein was added at the end of the polymerization process. It has been shown that the rhG-CSF was mainly adsorbed on the surface of the nanoparticles and most of the colony stimulating activity was conserved. Using precipitation of performed polyisohexylcyanoacrylate, 90% of rhG-CSF was associated with nanoparticles, the protein being mainly adsorbed onto the nanoparticle surface. In this case, a decrease of the colony stimulating activity was however observed. Whatever the method used, the in vitro release of rhG-CSF from the polyisohexylcyanoacrylate nanoparticles, was progressive during 8 h in seric conditions. Nevertheless, using mice as an animal model, it has been shown that the short-term effects of intravenously injected rhG-CSF were not increased by its association with polyisohexylcyanoacrylate nanoparticles.

Published
1998

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